This study addresses the challenge of selecting the best maintenance therapy for ovarian cancer patients. The two medications under consideration are PARP inhibitors and bevacizumab. The aim is to provide clear guidelines based on scientific evidence that can help oncologists make informed treatment decisions. Upon evaluating various options, it is recommended that bevacizumab be spared for a second line maintenance therapy, while PARP inhibitors should be offered to all advanced ovarian cancer patients who have responded to initial platinum-based chemotherapy. The findings emphasize the importance of ongoing research to identify additional factors that can predict the effectiveness of bevacizumab. By following these guidelines, healthcare professionals can improve the outcomes and quality of life for ovarian cancer patients, contributing to better overall management of the disease and its impact on society.Background: Maintenance therapy with PARP inhibitors and bevacizumab is approved for ovarian cancer treatment in the first and second line settings, but selecting the optimal sequence is challenging due to restrictions on using the same medication twice. This review aims to establish guidelines for ovarian cancer maintenance therapy based on the strength of scientific evidence, the most effective treatment strategy, and the impact on the healthcare system. Methods: Six questions were formulated to evaluate the scientific evidence supporting different maintenance therapy options using the AGREE II guideline evaluation tool. The questions address the acceptability of reusing the same medication, the efficacy of bevacizumab and PARP inhibitors in the first and second line settings, the comparative efficacy of these medications, the potential benefit of combination maintenance therapy, and the economic impact of maintenance therapy. Results: Based on the available evidence, bevacizumab should be preserved for second line maintenance therapy, and maintenance therapy with PARP inhibitors should be offered to all advanced ovarian cancer patients who have responded to first line platinum-based chemotherapy. Additional molecular predictors for bevacizumab efficacy are needed. Conclusions: The presented guidelines offer an evidence-based framework for selecting the most effective maintenance therapy for ovarian cancer patients. Further research is necessary to refine these recommendations and improve outcomes for patients with this disease. Bevacizumab is a monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), which is a protein that stimulates the growth of new blood vessels. By inhibiting VEGF, bevacizumab reduces the formation of new blood vessels that supply oxygen and nutrients to tumors, thus slowing down their growth and spread . In addiPARP inhibitors (PARPis) are a class of drugs that target poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. When PARP is inhibited, cancer cells with defects in other DNA repair pathways, such as those with BRCA mutations, are unable to repair DNA damage efficiently, leading to cell death ,4.PARPis and bevacizumab have been approved as first and second line maintenance therapies for ovarian cancer. However, due to drug registration limits, it is not possible to use bevacizumab after bevacizumab or PARP after PARP. This presents a significant challenge in selecting the best sequence of treatment. It is crucial to consider the varying strength of scientific evidence from published studies on ovarian cancer maintenance therapy in the decision-making process.Quality Assessment: The guideline should provide comprehensive details on the assessment of study quality and risk of bias for the included studies. This should encompass the tools or criteria used for evaluation;Evidence Synthesis: The guideline should clearly outline the methods employed to synthesize the evidence gathered from relevant studies; andRecommendations Formulation: The guideline should provide a clear description of the process used to formulate recommendations. This should include how the evidence was graded and how the values and preferences of the target population were taken into account.The objective of this review is to create a set of guidelines for maintenance therapy based on several factors including the strength of scientific evidence from available trials, the treatment strategy that offers the most benefits to patients, and affordability for the healthcare system. The guidelines were developed according to the standards set by the AGREE II  guideline evaluation tool. It comprises 23 items that are categorized into six domains, among which the rigor of development domain holds significant importance. Key points for the rigor of development domain include:In my approach, I primarily focus on addressing clinical questions by comparing the strength of scientific evidence derived from available data.The resulting guidelines aim to provide healthcare professionals with clear and evidence-based recommendations for maintenance therapy in a way that is both effective and cost-efficient.Most clinical trials on maintenance therapy in ovarian cancer provide results for the general population (confirmatory data) as well as post-hoc analyses (exploratory data). However, it is important to consider whether the strength of evidence for confirmatory data is the same as that of exploratory data in randomized clinical trials (RCTs).Confirmatory data analysis involves testing specific hypotheses or research questions that were formulated prior to conducting the study. The goal of confirmatory analysis is to establish whether the study’s pre-defined hypotheses are supported by the data or not. This approach uses statistical methods that are pre-specified before the start of the study.Exploratory data analysis, moreover, involves exploring the data without any preconceived notions or hypotheses. This approach is used to generate new hypotheses and insights from the data that were not previously considered .It is important to note that confirmatory analysis is more rigorous and reliable than exploratory analysis, as it follows a pre-specified protocol and has a lower risk of producing false-positive results. However, exploratory analysis can be useful for generating hypotheses and identifying potential trends or relationships in the data that can be tested in future studies .According to the GRADE system, which is widely used to evaluate the strength of evidence for clinical research, the grade of evidence for results of a phase III RCT can range from high to moderate, depending on the study design, methodology, and risk of bias. Conversely, the grade of evidence for exploratory data analysis would usually be lower and can range from low to very low, depending on the specific study design and methodology .In general, results coming from the exploratory data analyses of RCTs are equal in strength to the results of observational studies .In this review, the strength of scientific evidence was defined based on the guidelines for scientific evidence classification set by The Agency for Health Technology Assessment and Tariff System (AOTMiT) . See TabThis classification does not include network meta-analysis (NMA) which is a statistical method that allows for the comparison of multiple interventions and their relative efficacy and safety. NMA is an extension of traditional pairwise meta-analysis that can compare multiple interventions that may not have been directly compared in randomized controlled trials (RCTs). The strength of evidence in NMA is defined by SUCRA (surface under the cumulative ranking) values which depend on the quality of the underlying RCTs and the methods used to conduct the analysis. Strength of evidence of high SUCRA value indicates scientific evidence of IIB .To determine whether or not to “Bev” during ovarian cancer maintenance therapy, we have formulated six key questions that need to be considered in order to arrive at an informed decision:Several clinical trials have investigated the use of PARP inhibitors in patients with ovarian cancer who had received prior PARP inhibitor therapy. For example, in a phase II trial of the PARP inhibitor niraparib, patients who had received prior PARP inhibitor therapy had a lower response rate compared to those who had not received prior therapy . SimilarRegarding bevacizumab, there is evidence that its effectiveness may be reduced in patients who have previously received bevacizumab therapy. For example, a phase III trial of bevacizumab in patients with recurrent ovarian cancer (platin sensitive or platin resistant) showed that patients who had previously received bevacizumab had a shorter progression-free survival compared to those who had not received prior therapy ,14.In summary, while there is no direct evidence suggesting that PARP inhibitors cannot be used after prior treatment with other PARP inhibitors, there is some evidence suggesting that they may be less effective. Similarly, there is evidence suggesting that the effectiveness of bevacizumab may be reduced in patients who have previously received bevacizumab therapy.However, the use of these drugs in ovarian cancer treatment is determined on drug registration regulations limiting the usage of either first or next line settings.There was a total of two phase III randomized controlled trials (RCTs) testing the efficacy of bevacizumab in the first line ,16, and Confirmatory data analyses (ITT population) of GOG218, ICON7, AURELIA, OCEANS, and GOG213 have shown that Bev increases PFS in second line settings only ,15,16,17p = 0.12, I2 = 54%) [The increase of PFS observed in the first line for the high-risk group of patients  comes from exploratory data [strength of evidence IIIB] and is lower than the increase of PFS in ITT population of second line maintenance therapy   .Unfortunately, there is currently no available data to answer this question as there are no three-arm randomized controlled trials comparing the efficacy of the combination maintenance therapy (bevacizumab + PARP inhibitor) with bevacizumab or PARP inhibitor alone in the first line setting.The PAOLA-1 trial evaluated the addition of olaparib to standard first line chemotherapy and bevacizumab as maintenance therapy in patients with advanced ovarian cancer who responded to first line treatment. The trial found that the addition of olaparib to bevacizumab significantly improved PFS compared to bevacizumab alone, with a hazard ratio of 0.59  in the overall population   . According to the exploratory data from the PAOLA-1 trial, the combination of bevacizumab and olaparib may be more beneficial for patients without residual disease. However, it is important to consider that these trials involved different patient populations, treatment regimens, and endpoints, which could have contributed to the contrasting results. These conflicting results confirm the low-strength of evidence arising from exploratory data in clinical trials. It is important to await further confirmation from additional studies before drawing any definitive conclusions or making treatment decisions based solely on this exploratory data.A recent network meta-analysis (NMA) evaluated the use of different PARPi regimens in BRCA-mutated ovarian cancer patients who were responsive to front line platinum treatment  or those with platinum-sensitive relapsed cancer . The paper compared the clinical benefits, toxicity, and net health benefits of various regimens in phase III randomized controlled trials. The study revealed that the current PARPi regimens demonstrated similar clinical benefits, toxicity profiles, and net health benefits in both the upfront (front line) and relapsed settings. However, the addition of bevacizumab to olaparib was found to increase the cost per unit net health benefit compared to olaparib monotherapy. The upfront PARPi regimens were associated with lower toxicity scores compared to the regimens used at relapse. The authors of the paper concluded that combining PARPi with bevacizumab is not recommended in the upfront setting from a cost-effective perspective  [strengtThe current decision-making process to use bevacizumab in ovarian cancer is based on clinical features  from the exploratory analyses of GOG218 and ICON7 studies. However, this approach can lead us to overlook the importance of determining the VEGF expression or angiogenic profile of the tumor, similar to how BRCAm or HRD are used to determine eligibility for PARP inhibitors.A very recent study has validated the angiogenesis score, which could be used to stratify therapy response to tyrosine kinase inhibitors to provide evidence for patient-tailored oncologic therapy in ovarian cancer . This coBy assessing the angiogenic profile of the tumor, we can better identify patients who are more likely to benefit from antiangiogenic therapy, including bevacizumab. Therefore, it is important to consider the tumor’s VEGF expression and angiogenic profile when deciding whether or not to use bevacizumab in ovarian cancer treatment. Considering the cost and potential harm of such therapies, guiding angiogenic treatment reflects an unmet clinical need from a clinical and economic perspective. -Low strength of evidence supports the use of bevacizumab (Bev) in the first line treatment. It is recommended to preserve Bev for second line therapy; and-PARP inhibitors (PARPis) should be used as first line maintenance therapy for all patients who respond to platinum-based treatment.Based on a comparison of the strength of scientific evidence from available trials, it appears reasonable to consider using PARP inhibitors as first line maintenance therapy for all patients with advanced ovarian cancer who respond to platinum-based chemotherapy. For patients who do not respond to platinum or who experience recurrence during PARP inhibitor maintenance, bevacizumab may be more suitable as a second line option—it improves PFS and OS (confirmatory data). However, more trials are needed to validate the efficacy of bevacizumab in patients with molecularly confirmed angiogenic tumor profiles (bevacizumab predictors), regardless of the treatment line. The final conclusion of the manuscript provides detailed guidelines that can be summarized as follows:


The synthesis process used to obtain these powders was the polymeric precursor method (Pechini), at a temperature of 700 °C for 6 h. The characterization of the obtained oxide nanoparticles of interest revealed the presence of a majority perovskite-type phase with an orthorhombic In this research work, the photocatalytic capacity shown by the nanoparticles of the CaTiO Emerging pollutants (EPs) are synthetic or naturally occurring chemicals or biological pollutants whose presence in the environment is not considered significant in terms of distribution and concentration, so they tend not to be monitored ,2. There−1 to ngL−1 and rarely in mgL−1, EPs are capable of causing adverse effects in organisms 89], Ag , graphen6-TiO6 groups, or the presence of In this work, CTO-NPs were successfully synthesized using the Pechini chemical method at 700 °C with a reproducible, controlled methodology. From the XRD results carried out on the catalyst, the coexistence of two crystalline phases is concluded: a majority perovskite-type phase with a


Background and Objectives: Sinus tarsi syndrome (STS) is defined as pain located at the lateral opening of the tarsal sinus. The exact etiology of sinus tarsi syndrome is not completely understood. Some do not believe it to be a true pathology. This review aims to clarify the definition of sinus tarsi syndrome to better understand the underlying pathologies. We further propose an algorithm to evaluate sinus tarsi pain and provide advice for consecutive treatment options. Design: This is a narrative review. By searching PubMed, the available current literature was reviewed. Articles were critically analyzed to determine the pathoanatomy, biomechanics, and etiology of sinus tarsi pain. Algorithms for clinical evaluation, diagnosis, and treatment were also recorded. Finally, the authors approach to evaluating and treating sinus tarsi pain was included in this review. Results: Reviewing the available literature, STS seems to be a catch-all phrase used to describe any pain in this anatomic region. Many causes of sinus tarsi pain were listed, including impingement, subtalar instability, and many other pathologies around the ankle. Conclusions: A thorough evaluation of patients presenting with pain in the sinus tarsi or instability of the hindfoot is essential to determining the underlying cause. When the cause of pain is still not clear after clinical exam and radiologic assessment, subtalar arthroscopy can be helpful as both a diagnostic and treatment tool. We propose that the term of STS should be avoided and that a more accurate diagnosis be used when possible. Once a diagnosis is made, appropriate treatment can be initiated. Sinus tarsi syndrome (STS) is defined as pain around the lateral opening of the tarsal sinus and may include symptoms of hindfoot instability. This definition is broad and non-specific, and current literature fails to elucidate a clear cause of STS. Some authors have even questioned the existence of STS as a true anatomical pathology .The first description of STS was by O’Connor in 1958 . He consThe treatment of STS ranges from non-operative modalities, such as sinus tarsi injections with local anesthetics and corticosteroids, to surgical procedures including denervation, open and arthroscopic debridement of the sinus tarsi, and stabilization of the subtalar joint complex ,11,12,13Nevertheless, STS remains a topic of controversy. The condition is poorly defined, with no diagnostic criteria or clear treatment algorithm. Sinus tarsi pain may be a symptom of a wide range of underlying foot and ankle pathologies. This review aims to examine the current literature on sinus tarsi syndrome. We summarize the tarsal sinus anatomy, biomechanics of the subtalar joint complex, possible etiologies and differential diagnoses, the clinical work-up, and treatment options.In order to better assess the debate of STS and the etiology of sinus tarsi pain, a review of the available literature was performed in September 2022 using the PubMed database, searching the following keywords: “sinus tarsi syndrome”, “sinus tarsi pain”, “sinus tarsi impingement”, “sinus tarsi anatomy”, “subtalar joint”, “subtalar joint anatomy”, “subtalar biomechanics”, “subtalar instability” and “subtalar arthroscopy”. Titles and abstracts were screened for relevance by two independent reviewers.PRISMA guidelines were not applicable, as the design of this review was not defined as a systematic review but as a critical review. The primary aim was not only to identify articles that addressed sinus tarsi syndrome but also to screen for manuscripts that studied related topics. Full-text articles were retrieved, and their references were further searched for additional relevant studies and book chapters to supplement the electronic database searches. The available literature was summarized, and evidence on STS, including the anatomy, biomechanics, etiology, clinical evaluation, diagnosis, and treatment, was critically reviewed. The authors added an overview of the underlying anatomy, as well as their personal experience diagnosing and treating sinus tarsi pain, including illustrative cases.The talotarsal joint is subdivided into the subtalar joint  and the talocalcaneonavicular joint. The border between these joints is the tarsal sinus, or sinus tarsi. Morphologically, the talotarsal region has been described as being composed of three compartments: Anterior, middle, and posterior . The antThe tarsal canal and tarsal sinus contain a complex system of ligaments, arteries and their anastomoses, adipose tissue, joint capsules, and nerve fibers . The artThe cervical ligament (CL), the interosseous talocalcaneal ligament (ITCL), and three roots of the inferior extensor retinaculum (IER) are the main stabilizing structures found in the tarsal sinus and canal. The ligament complex of the tarsal sinus and the talotarsal joint are essential for normal movement and stability of the talotarsal joint  15,16].,16.15,16Other stabilizing ligaments include the calcaneofibular ligament (CFL), the anterior talocalcaneal ligament (ATC), and the bifurcate ligament  on the lateral side. Medially, there is the medial collateral ligament complex  and the anterior and posterior tibiotalar ligaments. On the plantarmedial aspect is the spring ligament complex . The posterior facets of the talus and calcaneus are larger than the middle and anterior facets. They are separated from the other two facets by the interosseous calcaneal ligament ,20.In the posterior compartment of the subtalar joint, the concave facet of the talus lies on the convex posterior facet of the calcaneus, forming the subtalar joint. The anatomy of the subtalar joint is extremely variable between individuals in terms of facet size and shape ,15,16.The sustentaculum tali is a prominent bony structure formed by the middle calcaneal facet and provides a sliding surface for the tibialis posterior, flexor hallucis longus, and flexor digitorum longus tendons at its plantar surface.The talotarsal joint, as already mentioned, is subdivided into the talocalcaneonavicular joint and the subtalar joint. It is morphologically a complex multiplanar joint with an oblique axis. The subtalar joint, or talocalcaneal joint, is a saddle-shaped joint and has a convex upward orientation. Its motion has been compared with a mitered hinge . The talThe unique composition of the talotarsal joint and the orientation of its facets allow for motion of the included bones in three planes. These movements together then define the range of motion for the talotarsal joint complex as 25–30° of inversion/supination and 5–10° of eversion/pronation ,24,25.The described triplane motion in combination with plantarflexion/dorsiflexion of the talocrural joint (ankle joint) is crucial for walking and adjustments to uneven ground. With the subtalar joint everted with the hindfoot in valgus, the transverse tarsal joints are “unlocked”, which allows a smooth transition from heel strike to stance phase. As gait progresses through the stance phase, the hindfoot goes into varus, and the subtalar joint inverts, “locking” the transverse tarsal joints, providing a rigid lever allowing propulsion forward .Numerous etiologies of STS have been proposed. In 1960, Brown suggested it was caused by pinching of the herniated synovial membrane in the tarsal sinus , and theInstability of the talocrural and talotarsal joints has also been described in relation to STS ,38. The Vascular causes have also been considered. Schwarzenbach et al.  publisheAkiyama et al.  describeGiven the multiple causes of sinus tarsi pain, a detailed medical history is required, including a thorough pain history. This should include questions about symptom duration and location, when pain occurs, ability to participate in sports, associated instability, history of previous trauma, and prior treatment or operations on the foot or ankle. A complete medical history to elicit other causes of hindfoot pain, such as infection, arthritis, and gout, should be obtained. All patients with STS symptoms report tenderness or pain in the sinus tarsi area. Distinguishing between ankle and subtalar instability is difficult because the clinical symptoms of both are very similar . In the A focused assessment and clinical examination of the foot and ankle, as well as an evaluation of gait, should be performed. Assessment of hindfoot alignment should be noted. Inspection for swelling, warmth, and redness of the hindfoot, as well as a thorough neurovascular exam, are imperative. Palpation of the sinus tarsi is essential, specifically with dynamic eversion to replicate impingement. Clinical measures of talotarsal range of motion can be challenging. Some have suggested that manual exam of isolated subtalar motion is not accurate since several joint complexes are involved during inversion and eversion of the foot and ankle . The keyTo date, there are no described pathognomonic signs or special tests to diagnose STS based on history or physical examination. However, the senior author’s dynamic impingement test is felt to be a strong clinical indicator for sinus tarsi impingement. This test is performed by everting the hindfoot and simultaneously palpating the sinus tarsi. In addition, pain relief after injection of local anesthetic or cortisone into the sinus tarsi is strongly suggestive of STS . InjectiAppropriate imaging of patients assumed to have STS is a critical part of determining the treatment algorithm. To evaluate malalignment and deformity, specifically to identify a potentially causative planovalgus foot, standing anteroposterior (AP) and lateral radiographs of the foot and ankle are necessary A. AdditiAs evaluation of the talotarsal joint on conventional radiographs is difficult, other radiographic techniques to visualize the talotarsal joint have been proposed. The Broden view is used to view the posterior facet in a lateral projection. The patient is supine with the leg internally rotated 30° to 45°. The center beam is placed in the lateral malleolus. The x-ray tube is then angled sequentially in 10-degree increments from 10 to 40 degrees cephalad ,25,44. AIf there is any evidence of a limb length discrepancy or rotational long bone deformity, a standing AP long leg radiograph and rotational CT scan of the legs are recommended, respectively.Stress radiographs performed by manual traction, or a Telos device, have been described to assess mechanical subtalar joint instability ,25. The Since talotarsal pathology is difficult to identify on X-rays, the use of cross-sectional multiplanar imaging is often recommended to better visualize the complex joint anatomy and improve the sensitivity and specificity of detecting subtalar joint pathology. Computed tomography (CT) imaging is the modality of choice if bony pathology is suspected, including arthritis, hindfoot malalignment, bony impingement due to elongated lateral talar processes , bony taSingle-photon emission computerized tomography (SPECT) has the benefit of marrying the image of a radioisotope bone scan with the cross-sectional imaging of a CT, allowing for a more specific analysis of areas of impingement and increased uptake ,52 FiguB.Magnet resonance imaging (MRI) of the hindfoot is commonly performed to evaluate talotarsal joint and soft tissue pathology, including sinus tarsi syndrome ,53. MRI Arthrography of the subtalar joint has been reported as a way of diagnosing sinus tarsi syndrome, but there are no clear criteria for pathological findings . ArthrogSubtalar arthroscopy allows for direct visualization of the joint and ligaments for accurate diagnosis and concurrent treatment. Arthroscopic evaluation of the tarsal sinus and the subtalar joint of STS patients can reveal tears of the interosseous ligament, cervical ligament, arthrofibrosis, and degenerative joint disease . A prospMost authors initially treat STS with non-operative modalities, including sinus tarsi injections with corticosteroids or local anesthetics, activity modification, and physical therapy ,11,28. TThe literature describes many clear pathologies and causes for pain around the subtalar joint and sinus tarsi. While these are often labeled as STS, the term STS is still frequently used to describe non-specific pain in the sinus tarsi area. In the authors’ opinion, STS will almost always have a causative pathology if one employs an appropriate and detailed history, physical exam, and radiographic or arthroscopic evaluation . The keyIf valgus hindfoot alignment or a planovalgus foot are noted, the resulting lateral bony and soft tissue impingement may be causing the sinus tarsi pain. Mechanical offloading the tarsal sinus is needed. Conservative treatment with corrective orthotics, physical therapy, and bracing can be trialed first. If symptoms persist, surgical deformity correction with bony and soft tissue procedures is needed.If subtalar instability is noted, physiotherapy, including dynamic stabilizer strengthening exercises, proprioception training, and bracing of the hindfoot, should be trialed. If this fails, lateral ligament reconstruction may be necessary ,21,62. IIf intraarticular subtalar pathology is not identified on imaging and conservative treatment is not leading to pain relief after a minimum of 6 months, subtalar arthroscopy should be performed ,21,58,62In the last decade, subtalar arthroscopy and sinus tarsi endoscopy outcomes have evolved dramatically with improved techniques, increased surgeon experience, and the development of specialized small joint instrumentation. Its use as a diagnostic and therapeutic tool for the evaluation and treatment of sinus tarsi syndrome is considered safe and effective. Compared to open techniques, it is reported to have faster postoperative recovery, decreased postoperative pain, and fewer complications . Frey etLi et al.  treated Since ankle and talotarsal instability often coexist  and are In conclusion, sinus tarsi syndrome (STS) is an imprecise term that is used to describe any sinus tarsi area pain. We recommend surgeons drop the term STS in exchange for the causative etiology, when identified, as this will dictate the treatment. Given that the evolution of sinus tarsi and subtalar arthroscopy allows for more detailed and accurate evaluation of sinus tarsi pathology, it can be used as an effective diagnostic tool that will allow concurrent management of pain sources. Whenever there is planovalgus alignment with subsequent sinus tarsi impingement, this should be treated accordingly. Subtalar or ankle joint instability is another differential diagnosis that can be treated successfully to relieve pain and symptoms.


N = 253). The quantitative results show that the mafia as a threat manipulation increased threat-related affective states in terms of higher behavioral inhibition (BIS) and lower behavioral activation (BAS). The qualitative results further depict proximal and distal defense mechanisms to reduce this threat, which can be categorized into models of threat and defense. Exploratory analyses indicate that naming distal defenses positively affected the increase of BAS. Additionally, when participants had higher levels of BIS after the threat, naming more defenses and proximal defenses positively affected the decrease of BIS. Further qualitative results provide valuable information on effective personal and societal buffers for the perceived threat of the Italian mafia.The present research investigated whether the Italian mafia as a Dark Triad threat increased threat-related affective states and explored how thinking about defense mechanisms may help to reduce these states. For this, we conducted a multi-method experimental study with Italians ( The Italian mafia includes the Cosa Nostra in the Western part of Sicily, the Ndrangheta from Calabria, the Camorra from Naples3, and the Apulian Mafia5. While these four organizations differ in terms of their history, symbolism, rituals, criminal interests, organizational structure, and modus operandi7, they show similarities in their ongoing violent strive for power5 for which they are frightened by the Italian population (e.g.9). However, research on the Italian mafia as a threat and how the population deals with the threat of the mafia to reduce their negative affective states is rare has not been researched. By investigating the mafia as Dark Triad (DT) threat, the present multi-method study gives valuable insights into people’s threat reaction to the mafia and their use of defense mechanisms to deal with the threat.The Italian mafia has gained significant notoriety as one of the prominent criminal organizations in Europe. The term “mafia” is hereby applied to groups and individuals who wanted to gain power over political and economic events in their city by threatening or using violence11. Such political violence is assumed to be connected to assassinations of and attacks on Italian politicians that significantly increase before and after elections12. In addition to controlling political decisions, the mafia also uses its power to control illicit trade, claim ill-gotten gains from economic actors, and control private economic activities13. The aim of infiltrating the economic system is to maximize their profit with rent extraction or laundering money. The large profits from illegal activities are invested in both illegal markets and the legal economy, which in turn allows the mafia to expand their political rule by penetrating and controlling legal sectors of the economy3. To gain control over a given territory and thus increase their political power in that area, as well as to establish contacts with legal entrepreneurs and penetrate the legal economy, the Italian mafia further does not recoil from techniques of extortion, such as demanding money or materials in exchange for protection15.Over the last decades, the Italian mafia has constantly exercised power to influence both the economic and political systems. For instance, it actively intervenes with violence to gain control over territories and further expand its political influenceBy using violence, attacks, or different techniques of assertion the Italian mafia has become famous for its ruthless and reckless behavior. Quotes attributed to (former) Italian mafia members further illustrate the mafia’s willingness to use force, such as “You can get much further with a kind word and a gun than you can with a kind word alone” (Al Capone) and “I can’t stand squealers, hit that guy!” (Albert Anastasia).16. This kind of behavior, such as relational devaluation , can be threatening to one’s basic needs, emotional well-being, and physical health18. Furthermore, such ruthless and reckless behavior to gain power can also be perceived as a Dark Triad threat19.Mafia members therefore resort to violence, murder, and/or other coercive and unethical means - a behavior that makes them rise in the command hierarchy or maintain their position of power22, as well as a high strive for power23. The DT is further related to abusive supervision, counterproductive work behavior, and bullying in the organizational context28, showing detrimental effects on subordinates and the organization41. Previous research shows that the mafia is connected to the DT: Imprisoned mafia members scored higher in psychopathy than non-mafioso imprisoners arrested for a similar crime42 and previous research has connected the mafia to narcissism46.The Dark Triad (DT) is a cluster of the three personality traits  that all share a decreased level of morality, agreeableness, and social emotions19. This change in affective states can be explained by the Reinforcement Sensitivity Theory: According to the General Process Model of Threat and Defense by Jonas et al.47, when people are confronted with an anticipated threat , they want to avoid it and are conflicted with what to do, leading to high vigilance, avoidance, and/or arousal. Thus, people confronted with an anticipated threat respond with a higher activation of the behavioral inhibition system (BIS)  and a lower activation of the behavioral approach system (BAS) 48. This process differs from people being confronted with an actual threat : Then the Fight-Flight-Freeze system (FFFS) sets on, leading to either flying out of the threating situation, fighting against the threat, or freezing/frighting/fainting as a kind of staying in an inhibited, hyper-vigilant, and hyper-anxious state49. The mafia as an anticipated DT threat  could therefore lead to higher BIS  and lower BAS  and as an actual threat (the mafia boss in front of me) lead to fight/flight/freeze/fright/faint.Due to its destructive and demoralized behavior, the DT can be perceived as a possible threat, leading to their victims’ alertness, anxiety, avoidance, and inhibition48. Figure If BIS activation can be decreased or BAS activation can be increased, the BAS instead of the BIS sets on, helping with concrete or abstract solutions. This BAS activation leads to different distal defense mechanisms that can either directly deal with the threat , such as by doing something against the mafia, or it can indirectly deal with the threat , such as thinking about better times. Such abstract and concrete distal defenses cannot only be on a personal level as the examples showed but also on a social level: In other words, regarding a concrete defense, other people, such as family members or institutions, can be involved in the defense, or regarding an abstract defense, shared worldviews can be involved45) we used the Italian mafia as a DT manipulation controlled by a DT manipulation check. Given that the DT can be perceived as a threat, increasing BIS and lowering BAS (e.g.19), we further hypothesized that this manipulation leads to this respective change in affective states. As thinking about defense mechanisms after a threat should again decrease BIS and increase BAS (e.g.50), we further expected a shift back. Thus, our first research question concerns the measured change in BIS and BAS after the mafia DT threat (Research question 1), concluding with the following two hypotheses:To summarize, the mafia can be a DT threat, which could lead to higher BIS and lower BAS activation as well as proximal and distal defense mechanisms. To explore this assumption, the present research investigated whether the mafia as a DT threat leads to higher BIS and lower BAS activation, and how people deal with this threat when it comes to defense mechanisms. As the mafia could be considered as DT . For this question, we inductively qualitatively analyzed the defense mechanisms people used after being confronted with the mafia DT threat as well as categorized them into the General Process Model of Threat and Defense47. This multi-method research approach gives valuable insights into how people react to the mafia perceived as a DT threat and which defense mechanisms can be used to effectively reduce this perceived threat.Lastly, a third research question qualitatively conducted possible buffers for such a threat situation. In other words, we investigated the societal and personal resources that could help to buffer the DT threat of the Italian mafia (Research question 3), as the process from threat to defense can be buffered by the situational and personal contextSD = 2.67) of the 12 statements were clicked on. The inductive qualitative data analysis revealed that the Italian mafia is perceived to be present in Italy (n = 236), although it was described by some participants to be less visible now than in the past (n = 35). Especially the mafia’s demand for protection money and threats were often mentioned by the participants (n = 196) but also its infiltration into the social and political system (n = 79), negatively affecting the Italian economy and society  (n = 82) and leading to a corrupt report system (n = 38). This made participants feel scared (n = 172), angry (n = 86), helpless (n = 82), inhibited (n = 51), alone (n = 19), and frustrated (n = 46). Furthermore, the Italian mafia was described as a criminal and deadly organization (n = 49). Hence, considering both the quantitative and qualitative results the manipulation of this study worked well and the mafia was perceived as DT threat.To check whether the mafia was perceived as a DT threat in our sample, we analyzed both the DT statements and the open answer fields see “” sectionF = 54.93, p < 0.001, η2 = 0.18, as well as BAS levels, differed between the measures , F = 77.51, p < 0.001, η2 = 0.24. As depicted in Fig. H1a and H1b, BIS increased, F = 81.38, p < 0.001, η2 = 0.25, Mbefore Threat = 4.22 (SD = 2.38), Mafter Threat = 5.38 (SD = 2.37), and BAS decreased after threat, F = 104.50, p < 0.001, η2 = 0.29, Mbefore Threat = 5.80 (SD = 1.61), Mafter Threat = 4.65 (SD = 1.96). In line with H1a and H1b, after the defenses BIS decreased, F = 22.37, p < 0.001, η2 = 0.08, Mafter Defenses = 5.04 (SD = 2.36), and BAS increased, F = 15.23, p < 0.001, η2 = 0.06, Mafter Defenses = 4.88 (SD = 1.98).Two repeated measures ANOVAs with a Greenhouse–Geisser correction showed that BIS levels, 47. As depicted in Table n = 105; #23: “I would denounce it whatever it takes”), be afraid , and give in/acquiesce everything . Based on the responses, which included a variety of fight, flight, and freeze/fright/faint strategies, we decided to further categorize them into the FFFS as part of the Reinforcement Sensitivity Theory49, although the FFFS should only be triggered in an actual threat situation involving fear51. By categorizing the responses into the FFFS, we were able to discover an additional defense mechanism that can neither be described as fight, flight, or freeze/fright/faint. We have described it as ‘giving in’ as succumbing to the demands of the mafia (n = 31).At first, the defense mechanisms were qualitatively analyzed and categorized into the General Process Model of Threat and Defenser =  − 0.43, p < 0.001). Furthermore, BIS (quantitative measure) was associated positively with the number of qualitative answers for proximal defenses and negatively with the number of qualitative answers for distal defenses, with a significant association between BISafter Threat and naming proximal defenses. Similarly, BAS was positively correlated with naming distal defenses and negatively with naming proximal defenses, with a significant correlation between naming distal defenses and BASafter Defenses.As shown in Table z-standardized BISafter threat or BASafter threat as covariates. As presented in Table distal defenses and, in particular, personal distal defenses had a significant positive effect on BASafter threat. In other words, the more distal defenses and, in particular, personal distal defenses were named, the higher the increase in BAS. The other defense mechanisms did not significantly influence the changes in BIS or BAS.To exploratively investigate what kind of defense mechanisms might have influenced the change in BIS and BAS after the threat to after writing defenses, we ran a series of regression analyses using different defense mechanisms as predictors and the 52, we further examined the moderating role of BISafter threat or BASafter threat in the relationship between the defense mechanisms named and BISafter defense or BASafter defense. As shown in Table after threat moderated the effect of the sum of defenses, proximal defenses, arousal, and freeze/fright/faint on BISafter defense, meaning that participants with higher levels of BISafter threat in comparison to those with average or lower levels experienced a significant decline in BIS from after the threat to after writing defenses when they named more defenses and, in particular, more proximal defenses. Additionally, we found that BASafter threat moderated the relationship between give-in and BASafter defense, meaning that participants with lower levels of BASafter threat experienced a stronger increase in BAS from after the threat to after writing defenses when they named more of giving-in defenses.Based on a repeated measures model approach according to Wan47, we further qualitatively inductively investigated which societal and personal resources could help to buffer the DT threat of the Italian mafia. About half of the participants expressed trust in the police and suggested reporting the threat , while others wished for more effective law enforcement and legality in politics . Participants further mentioned the important role of information . In addition, participants called people to support social movements against the mafia, such as Addio Pizzo or Libera . Moreover, they encouraged people to refuse to pay  and ask for help . Contrariwise, a few people suggested flight (n = 39), such as “mov[ing] to another state” (#16/#62/#69/#94/#108/#115/#126/#129/#171/#192/#208/#215/#225). Further mentions included the importance of job creation to reduce poverty and create alternatives for joining the mafia , the importance of psychological support , and the importance to “stop idolizing the mafia” (#51).As the process from threat to defense can be buffered by the situational and personal context9. However, research on how the population deals with the threat of the mafia is rare. Building on previous studies that showed a link between the mafia and DT tendencies (e.g.45), the present multi-method research explored (1) whether the mafia perceived as a DT threat is leading to higher BIS and lower BAS activation (quantitative approach), (2) how people deal with this threat when it comes to defense mechanisms as well as how this relates to BIS and BAS activation (mixed-method approach), and (3) what could be done on an individual and societal level to buffer the perceived threat .The Italian mafia is known for its ruthless and reckless behavior, for which they are frightened by the Italian population50).Concerning Research question 1, the results of this study showed that BIS increased and BAS decreased after the threat of the mafia as well as BIS decreased and BAS increased after thinking about the defense mechanisms. This result is in support of our hypotheses H1a and H1b as well as in line with previous threat research . Another explanation of this finding is the dual concern model that suggests five ways of how people deal with a conflict: (a) to compete, force and fight, (b) to compromise in terms of finding a deal or collaborate in terms of finding the best solution for both parties, (c) to avoid the conflict, and (d) to accommodate / give in. This last strategy of giving in is mainly used when there is a higher concern towards the other party than towards one’s own goals57—particularly when this party is powerful: “Accommodation often occurs when there is a power differential between the parties and the high power party is willing to use a forcing approach to obtain what he or she wants. Realizing that the situation is futile, the low power party accommodates to the high power party, limiting any damage to the relationship or the organization”58 (p. 72).Furthermore, one personal distal defense mechanism, i.e. “giving in”, was named that cannot be categorized into the FFFS47). By taking a closer look, we further found that naming more distal defenses and, in particular, more personal distal defenses seemed to help increase BAS. This finding is in line with the model, as personal concrete distal defense strategies help regain “personal control or self-efficacy [as well as can] provide a vision of clear and decisive goal pursuit”47 (p. 247). In addition, we found that people with higher levels of BIS had success in decreasing their BIS when writing about more defenses in general, independently of what they wrote about. This underlines the importance to exhibit a variety of defense mechanisms when dealing with negative affective states (e.g.60). By looking more closely, also naming more proximal defenses reduced participants’ BIS. Thus, writing about their BIS affective states seemed to have helped them feel less anxiously inhibited. Following previous clinical and non-clinical research on the effects of the expression of negative affective states, it can be supposed that the writing has led to enhanced self-acceptance, fostered self-understanding, and reduced inhibition of negative feelings, which, in turn, goes along with reduced feelings of stress (e.g.62). Additionally, we found that writing on giving in has helped people who felt lower levels of BAS after threat to increase their approach-oriented affective state. Although affective states can influence motivations and conflict strategies63, it is unclear why such a strategy where one gives up their control in some sense  can help BAS to regenerate. However, when looking at concrete personal defenses, such defenses do not need to be effective to work and as “compulsive reactions may also conflict with own goals and values” (p. 247) as can be seen by drug use or greedy consumption after threat47. In other words, giving in might just be an easy strategy people in their first impulse strive towards.Regarding the mixed-method part of Research question 2, we firstly discovered a positive relationship between BIS and proximal defenses, as well as a negative relationship between BIS and distal defenses. Similarly, we observed a positive relationship between BAS and distal defenses, as well as a negative relationship between BAS and proximal defenses. This finding is in line with the General Process Model of Threat and Defense see Fig. 47. By ta66). Further suggestions for buffers include sharing information about the Italian mafia with the public and supporting movements against the mafia. Previous and recent social movements, such as the Fridays For Future climate protest, have emphasized the valuable opportunities social movements offer by building powerful collectives, raising awareness for the threats, and motivating policy changes before the threatening circumstances even increase (e.g.69).In terms of possible societal and personal buffers (Research question 3), most people suggested going to authorities, while others criticized that more effective law enforcement and legality in politics are needed. This finding highlights the importance of trust in political actors to keep a political system stable, especially when citizens feel threatened . Thus, future studies should investigate other national or international contexts. A second limitation addresses the use of a scenario as manipulation, as affective states elicited by scenarios can differ from the affective states experienced in a field study design (e.g.74). For instance, a recent study by Baraldi et al.8 showed the associations between the mafia’s organized crime infiltration and women’s reduced participation in politics due to feelings of fear. A third limitation concerns our mixed-method analyses with our defense strategies; future research could focus on replicating our findings by measuring possible defense mechanisms quantitatively to better conclude the relationship of these defense mechanisms to the affective states. A fourth limitation addresses the use of a dichotomous scale for the DT manipulation check, as a Likert scale could better quantify the perception of the mafia as a DT threat.Although the present research provides valuable findings, there are some limitations to consider. One first limitation of this study is its use of an Italian study sample and its restricted focus on the Italian mafia. However, the Italian mafia’s activities are not limited to Italy9) highlight the feelings of anxious inhibition and fear triggered by the Italian mafia. However, our results depict the importance of writing about possible defense mechanisms to reduce these threat-related affective states. One practical implication could therefore be to not only inform about the mafia but also inform about how important it is to think about various defense mechanisms. Teaching citizens to use concrete personal defenses might be especially important to increase their feelings of BAS. Furthermore, our results provided valuable starting points for societal interventions to buffer the process from threat to defense.In conclusion, the Italian mafia as a DT threat and their effect on the Italian population cannot be denied: Not only our results but also the first field studies on the Italian mafia . Supplementary Appendix n = 1), not answering the open fields seriously (n = 2), and failing the reading check (n = 1) (a reading check was provided where participants had to write “party [festa]” in order to pass the reading check).The sample of this study consisted of 252 Italian people  who were between 18 and 59 years old  in the Italian language was sent out via social networks and via MTurk [There was no difference in the participants ‘answers when controlling for this variable as well as no time differences with regard to completing the survey. Participants recruited via Mturk received 1 Euro for their participation]. The survey can be found under the OSF link provided (see Data Availability Statement). The research was promoted as an online study investigating feelings and perceptions with regard to institutions. The survey started with agreeing to an informed consent, followed by BIS and BAS affective state measures. Then, the mafia threat was introduced and participants were asked about their perception of the mafia. Next, BIS and BAS affective states were measured again. After this, questions on defense mechanisms were asked—again followed by BIS and BAS affective states measures. In the end, demographic data, questions about participants’ Covid-19-related fears (as data was collected in 2021), and the possibility to leave a comment were collected. On the thank-you page, participants were debriefed.50): (1) How prevalent is the Mafia in Italy? (2) What do you think about the Mafia in Italy? (3) Take two minutes to imagine a situation in which you receive a threat from the mob. Then, take the time to write down what you imagined in this situation. Explain the situation in as much detail as possible. (4) Take time to imagine how that situation would make you feel. Then, take time to describe your feelings and emotions related to that event. (translated version).To make the DT threat salient, participants reflected on the mafia in Italy with regard to four open fields in a way of how a threat has been manipulated as a common practice in threat research , we used yes or no as answer options instead of a Likert scale. This way, we can better categorize the mafia as either a DT threat or not . The scale had an acceptable internal consistency of α = 0.69.A first manipulation check was the qualitative analysis of the open questions on the mafia to see whether it was perceived as a threat. To specifically address the DT aspect of the threat, we adapted the twelve items of the inhibited, worried, restless, and insecure. The first three items have been already used by other scholars , we further decided to add the item “insecure” to our scale (α = 0.91–0.93). To assess BAS, we used the items relaxed and cooperative by Greenaway et al.82 for measuring low approach orientation as well as an adapted version for measuring high approach orientation based on Greenaway et al.82 and Reiss et al.80 . Based on Greenway et al.82 participants were asked to indicate the extent to which this series of adjectives describe their current feelings from 1 (fully disagree) to 10 (fully agree). An overall score was computed for BIS and BAS as an average of all four or six items . Participants were asked to share their sense of agreement from 1 (fully disagree) to 5 (fully agree) to seven statements, such as “I am frightened about my body being in contact with objects contaminated by the coronavirus”. As this measure is out of the scope of the present research questions, it was not considered in the following analyses.For research outside the present study, we further collected data on participants’ Covid-19-related fears using the MAC-FR scale by Schimmenti et al.84 using the packages afex85, psych86, and lm.beta87. For the mediation analyses the macro PROCESS88 (model 1) was used. QCAmap was used for the qualitative analysis of the defense open questions. The eight steps of the inductive category development according to Mayring89 were conducted: (1) Two inter-coders were introduced to our research questions and information on the theoretical background of the research topic was given. (2) The selection criteria, the category definitions, and the level of abstraction (low) were explained to them. (3) The coders worked through the open answers given by the participants and extracted categories from them. (4) After working through 10% of the text materials a revision was made. (5) Afterwards, the text materials were completely worked through. (6) Main categories were created with regard to the Anxiety-to-Approach model; (7) then, an inter-coder agreement check followed. The coders’ results were compared and adjusted. To ensure high reliability, a subcategory was coded only if both coders agreed. (8) In the last step, a review of the final results, the calculation of the frequencies of the extracted categories, and the interpretation of the data followed.All quantitative data analyses were performed with RThe study was included in the FWF project FWF P 27457 and all studies in this project were approved by the Ethics Committee of the University of Salzburg.Supplementary Information.


There is a clear need for research evidence to drive policymaking and emergency responses so that lives are saved and resources are not wasted. The need for evidence support for health and humanitarian crisis is even more pertinent because of the time and practical constraints that decision-makers in these settings face. To improve the use of research evidence in policy and practice, it is important to provide evidence resources tailored to the target audience. This study aims to gain real-world insights from decision-makers about how they use evidence summaries to inform real-time decision-making in crisis-settings, and to use our findings to improve the format of evidence summaries.This study used an explanatory sequential mixed method study design. First, we used a survey to identify the views and experiences of those who were directly involved in crisis response in different contexts, and who may or may not have used evidence summaries. Second, we used the insights generated from the survey to help inform qualitative interviews with decision-makers in crisis-settings to derive an in-depth understanding of how they use evidence summaries and their desired format for evidence summaries.We interviewed 26 decision-makers working in health and humanitarian emergencies. The study identified challenges decision-makers face when trying to find and use research evidence in crises, including insufficient time and increased burden of responsibilities during crises, limited access to reliable internet connection, large volume of data not translated into user friendly summaries, and little information available on preparedness and response measures. Decision-makers preferred the following components in evidence summaries: title, target audience, presentation of key findings in an actionable checklist or infographic format, implementation considerations, assessment of the quality of evidence presented, citation and hyperlink to the full review, funding sources, language of full review, and other sources of information on the topic. Our study developed an evidence summary template with accompanying training material to inform real-time decision-making in crisis-settings.Our study provided a deeper understanding of the preferences of decision-makers working in health and humanitarian emergencies about the format of evidence summaries to enable real-time evidence informed decision-making.The online version contains supplementary material available at 10.1186/s12913-023-09302-0. Research has shown that the scientific evidence does not always have a large influence on decisions in health and humanitarian emergencies primarily because of the format it is presented that is not conducive for real-time decision-making in crises.The need for evidence support for health and humanitarian crisis is even more pertinent because of the time and practical constraints that decision-makers in these settings face.These findings contribute to recognized gaps in the literature and practice, including preferences of decision-makers working in health and humanitarian emergencies about the format of evidence summaries to enable real-time evidence informed decision-making.This is the first study to produce an evidence summary template conducive for evidence informed decision-making in health and humanitarian emergencies and an example of an application of the summary to a real-world health and humanitarian emergency.Crises like the COVID-19 pandemic, climate related crisis  and the refugee crisis  are placing a strain on healthcare services, resources, and healthcare workers. The unprecedented scale of investment in strengthening health systems has led many stakeholders to demand the use of more reliable evidence for decision-making to ensure that desired impacts are achieved at acceptable costs . There iFor the purpose of this study, we define research evidence as the output of research that has been conducted in a systematic way and reported in a transparent manner . Our defFor the purpose of this study, we define evidence summaries as a short summary of the best available evidence stemming from secondary research based on a defined question. To date, there is no agreed upon evidence summaries template to support decision-making in crises. There are several organizations that develop and disseminate evidence summaries curated for decision-making in crises. For example, Evidence Aid is a non-profit organization that specializes in collating and summarizing evidence about how to effectively prepare for and respond to disasters and emergencies . There aResearch evidence on the usefulness and effectiveness of evidence summaries to inform decision-making in crisis zones is lacking. The broader literature supports the use of rapid evidence summaries to inform decision-making in other settings –22. A crWe used a sequential mixed method study design. This type of design combines elements of qualitative and quantitative research approaches to ensure that we arrive at the breadth and depth of understanding on the use of evidence summaries to inform decision-making in crises. First, we used a survey to identify the views and experiences of evidence summaries by decision-makers who were directly involved in crisis response in different contexts. Second, we used the insights generated from the survey to help inform qualitative interviews with decision-makers in crisis zones to derive an in-depth understanding of how they use evidence summaries and the desired format of evidence summaries to gain real-time support in using evidence to inform decision-making. The reporting of this study followed the checklist for mixed methods research manuscription preparation and review .Decision-making processes are complex, especially when dealing with health and humanitarian emergencies where the need to make real-time decisions is imperative and often requires a network of stakeholders with different types of expertise. We purposively sampled participants who have used evidence summaries before, and those who have not. We aimed to survey and interview a diverse group of decision-makers from various countries working in different crises, with a wide range of experience working in health policy and management decisions. For inclusion, participants had to belong to one of the following five categories based on their roles in decision-making in crisis response and where appropriate, across the humanitarian aid, health system, and health research system sectors: 1) senior decision-makers’ ; 2) field managers  directly involved in coordination and management of crisis situations; 3) healthcare providers  involved with either the development of medical guidelines in crisis situations or directly delivering medical care to people in crisis situations; 4) advisors directly involved in advising about policy development and implementation strategies; or 5) analysts and researchers directly involved in responding to research evidence requests from the previous four categories of participants.A two-stage sampling approach was used to identify and recruit key informants , 25. TheWe aimed to complete at least 5 survey respondents and semi-structured interviews for each type of participant category  for both evidence summary users and non-users, while recognizing that this estimate was dependent on the availability of appropriate participants.Participants completed an online survey administered using Lime Survey (survey instrument available as an e-appendix). The survey was in English language and consisted of four parts with the first part focusing on participants background and demographic characteristics, the second part related to questions that captured participants’ research experiences and familiarity with evidence summaries, the third part specific for evidence summaries users experiences and preferences, and lastly questions directed at non-evidence summary users reasons for not using evidence summary websites and preferences for evidence summaries and platform hosting summaries. We aimed to have the same preference questions for both users and non-users. However, non-users were not as familiar with evidence summary websites and therefore, we had to slightly adapt their preference questions, which limited our ability to compare some of the preferred features between the two groups.Following completion of the survey, interviews were conducted via Zoom and lasted approximately 30 min. Interviews were conducted by the PI  who holds a PhD in Health Policy and has experience in conducting semi-structured interviews. Interviews were also conducted by other members of the research team (Parakh) who received training by the PI. Interviews were audio-recorded after receiving informed consent from the participant, audio recordings were transcribed verbatim, and the written transcriptions were used for data analysis. Potentially identifying information  was removed at the time of transcription. We conducted the interviews in English, which is the language all our participants preferred to conduct the interview in. A pilot interview with a research team member was conducted to refine the interview questions. The questions began by asking individuals about their roles and experiences related to their research evidence needs to support decision-making in crises. For example, questions were asked around what type of information influenced their decision-making process, what sources of research evidence they use, and their knowledge of evidence summaries. The interview then focused on specific questions related to evidence summaries and the platforms on which they are hosted. We also showed participants an example of an evidence summary retrieved from Evidence Aid website to solicit their feedback on it.A mixed methods approach to data analysis was employed. For the survey, quantitative data was summarized using simple descriptive statistics . Data analysis included calculating descriptive statistics related to all assessed measures, including background of participants, their experiences with evidence summaries, and their attitudes towards using them. For the semi-structured interview data, we used a deductive framework analysis approach towards our collected data , 27. FraOur results section starts with a brief description of the key informants we surveyed and interviewed to arrive at a comprehensive understanding of the views and preferences of decision-makers with rapid evidence summaries to support real-time evidence informed decision-making in crisis settings. We then describe the preferences of evidence summary users and introduce an evidence summary template based on the insights gathered.. Participants participating = Twenty-six. Table We recruited 16 participants from our first stage of sampling, and 10 additional participants were identified through snowball samplingConcise summary of the evidence, including benefits, harms and costs, and implementation considerations and recommendations”, “A link that directs you to the full text source”, “Full text pdf option”, “Assessment of the quality of the evidence”, and “date of search strategy ”.Table “Having access to full text”, “Having a concise summary”, “Including information about the research methods”, “Having infographics”, and “Including quality assessment of the evidence”. When asked about features that would help them choose which evidence summary website to refer to, the majority reported credibility as the main factor (64%). Finally, the majority of non-users reported that they anticipate using evidence summaries in the future (64%), and more than half of them (57%) stated that information from these summaries might moderately influence their future decision making.Fourteen participants had no prior experience of using evidence summaries. They either did not have a specific reason for not using evidence summaries or had never heard about them before. Non-users indicated the following preferred features within an evidence summary: It’s not easy to access information in the midst of a crisis, you have a lot of research, I don’t want to wait long so I use my technical advisor within the technical team that are based in my country level who then can dig into the information and make sense of what might be useful for me.” – Evidence summary user 1“Two key themes emerged from our interviews on preferred sources for obtaining information in a crisis. First, there is a reliance on internal sources  to obtain relevant information. Decision-makers we interviewed discussed the benefits of having in-house technical advisors who can retrieve contextually relevant information stating:When you need evidence and information right away, Google can give you that immediately. Journal articles don’t provide that type of information right away”– Evidence summary user 2“Second, Google and Google Scholar were repeatedly cited as a key source for obtaining research evidence in crises. A key informant stated that the reasons behind frequently using Google and Google Scholar is because they are:Filtered information on a trustworthy site” Non-evidence summary user 1“Our interviews with participants provided us with additional challenges participants face in finding and using research evidence in crises. First, the lack of time and increased burden of responsibilities during crises creates a challenging environment to find and use relevant evidence to inform decision-making. A key stakeholder working in crisis settings at a non-governmental agency highlighted how the lack of time to find information makes it imperative to find:In crises, there are often internet connectivity download issues especially with large documents. Halfway through browsing, everything can stop, and you don’t have the bandwidth, or the quality of connection is reduced which means you have to redo the search all over again.” – Evidence summary user 1“Second, there are challenges with having access to reliable internet connection that would enable download of large documents with one decision-maker stating:“We have a lot of data points. Technical units collect massive amounts of data that includes numbers on people, numbers on meetings, numbers on sites. What they haven’t been able to do is to partner with say academic to do analysis of the data and to conduct impact studies.”– Non-evidence summary user 2Third, challenges arise in regard to the large volume of available data that is not analyzed and translated into user friendly summaries. For example, a decision-maker stated the following:Most of the people who are in the field working in crises do not rely on scientific and evidence-based data in their work, instead they rely on lessons learned and what they have seen in their careers.” – Evidence summary user 3“Lastly, decision-makers working in organizations that carry out field operations in crises highlighted that research evidence, as defined in this study, is not considered a main source of information for operational teams. Instead, lessons learned and tacit knowledge are the main sources of information:Before COVID-19 I would go to the CDC or FEMA website and was able to find one single source of evidence on there but during COVID-19 I would go on the same site and there would be 20 different web pages about the same topic.” – Evidence summary user 3“Participants noted that during the COVID-19 pandemic, there was a plethora of different websites on the same topic making it challenging to find and use evidence in real-time to inform decision-making. One decision-maker stated:There is a difference between finding and using evidence pre-pandemic and post-COVID-19 pandemic. During the pandemic everything was slow, and it was hard to find the relevant evidence because it was either not available or rapidly changing” – Evidence summary user 4“Decision-makers also noted that finding and using research evidence to inform decision-making during the COVID-19 pandemic was a slow and tedious process given the rapidly emerging evidence, with one decision-maker stating:A lot of the online resources for evidence were much more health-specific focused, and less so on preparedness and mitigation efforts. What we really needed and couldn’t find much of is evidence around the protective actions we need to take, the types of policies we should implement, and what are the population level impacts from the virus and less so on clinical interventions and symptomatology of the virus” – Evidence summary user 4“A senior decision-maker working in emergency preparedness and response at a government agency also noted that during the COVID-19 pandemic, there was little information available on evidence websites specifically around preparedness and response measures. Most of the available evidence was focused on clinical interventions and clinical pathways of the virus. As stated by that decision-maker:“If you’re reading something on Cochrane or Evidence-Aid website, you would expect that is something of good quality and that you can trust the evidence presented” – Evidence summary user 5Several features of online websites hosting evidence summaries were cited by participants as important facilitators of real-time evidence use in crises. First, the credibility of the evidence summary website is a main factor in deciding whether to use the site to find and use research evidence summaries. This is partly because of the lack of time to navigate a new site, but also because of concerns around the quality of evidence presented. A participant we interviewed highlighted this by stating:If it is not free of charge, then it is not useful. The whole objective is to make sure people can access evidence on a timely basis to inform their decision-making, so if you are putting a restriction of having to pay to access the evidence summary then it is defying the objectives of ensuring timely evidence informed practice” – Non-evidence summary user 3“Second, the ability to access online websites of evidence summaries free of charge is a key facilitator with one decision-maker stating:figuring out which topic my question that I need answers for falls under”. Advanced filter features that allow decision-makers to filter the searches by region, crisis type, phase of emergency response, different disaster response sectors, etc., are a useful tool noted by decision-makers.A clearly searchable scheme where we can search by key terms is important. For example, being able to search by phase of emergency management, preparedness or mitigation versus response and recovery, entities involved in the response whether they are more transportation-related, health-related or school-related.” – Evidence summary user 3“Third, the ability to search by topic is considered a useful feature of online websites. Participants noted the need to categorize findings according to crisis types, population, or an intuitive crisis relevant framework. One of the challenges noted by decision-makers on categorizing summaries based on topics is “One of the most important things that I care about is language availability. This is because of the contexts and regions we work in. If I have to inform the Minister of Health from one of our member states, then the summary needs to be in the language of that member state” – Evidence summary user 5“Fourth, the linguistic accessibility for the online website and the summaries was cited as important. A decision-maker emphasized the need for the availability of multiple language summaries stating:Evidence Aid improved a lot in terms of accessibility. The site is now simpler with less information and better organization. This makes it more in line with the norms and regulations of Web accessibility. However, I want to emphasize the need for platforms to be more inclusive in terms of accessibility standards. It’s not an expensive task, it just requires continued support from the organization” – Evidence summary user 5“Fifth, participants prefer online websites that follow web accessibility norms and regulations. Web accessibility means that websites providing evidence summaries are designed and developed so that people with disabilities can use them. This means that people can perceive, understand, navigate, and interact with the Web. A decision-maker noted Evidence Aid’s web accessibility gradually improved gradually over time:Given that we work in crises, we do not have the time to go and conduct research and look deeper for proper sources so having access to websites where it is clear what the focus of the site is and having access to reliable information on the site that is easily accessible is very helpful” – Non-evidence summary user 3“Sixth, decision-makers prefer online websites that clearly explain on the homepage what the site is focused on and provide clear instructions on how to navigate the site to arrive at evidence summaries. A participant highlighted this by stating:Subscription option is an important feature where we can receive notification by email if there is any new research or new update available on the evidence especially during the COVID-19 pandemic” – Non-evidence summary user 4“Lastly, researchers responding to the knowledge needs of decision-makers noted a preference for an alert function on online platforms where they can receive email notifications if there is new research or newly updated evidence summary with one researcher stating:Overall, our participants view evidence summaries as helpful tools to inform real-time decision-making with one decision maker stating:“When I need that quick review of the current evidence then evidence summaries are awesome – they are great”– Evidence summary user 6Publicize that they produce evidence summaries, and they should engage with humanitarian organizations and actors through a communication strategy to disseminate the evidence summaries”– Non-evidence summary user 3“Some non-evidence summary users noted that part of the reason they are not using evidence summaries is that they did not know they exist. A decision-maker we interviewed highlighted that organizations that are producing evidence summaries should:In my role (as a senior decision-maker), I am looking for a clear answer. I work in emergency response, and I want the evidence presented in clear bullet points.” – Non-evidence summary user 5“A consistent theme identified was that evidence summaries should be presented in a clear, succinct, and action-oriented format . A senior decision-maker highlighted this by stating:The simpler the evidence summaries are, the easier it will be to digest.”– Evidence summary user 1“Decision-makers also noted the need for evidence summaries to be written in simple, jargon free language with a decision-maker stating:With a novel incident like COVID-19 the evidence was fast changing and as the incident (COVID-19 pandemic) progressed along, there were changes. For example, the evidence around face masks was changing in real-time and we did not know whether we should be promoting its use in the community. A chronological timeline of how evidence is changing over a period of time helps us to tell a story as to why we chose which interventions at what time, and so we can really measure whether our strategies are working or not, but it also ensures that we know what the most current evidence is because it’s otherwise tough to sort through and sift through it all”– Evidence summary user 3“Decision-makers noted a preference for presenting the chronological timeline of changes in the evidence with one decision-maker indicating:For COVID-19 pandemic, the evidence was quickly changing, and I needed to know from the evidence summary if the information was the most up-to-date to make sure that the answer presented in the summary is still valid for today” - Non-evidence summary user 6“Decision-makers also indicated a preference for the date of search strategy clearly highlighted. This was a particularly prominent finding when interviewing decision-makers that worked in COVID-19 pandemic response stating:Figure “It is very important to know who the target audience for the evidence summary because it differs if the summary is written for researchers as opposed to field staff working in operations who wants the evidence presented in a specific format.”– Evidence summary user 2Identifying the target audience for the evidence summaries was cited by key informants as an important element when drafting summaries. One researcher with experience in creating evidence summaries stated:You need that little, short sentence that tells you how this summary applies to you so that you can decide whether you want to go to the key findings or not. Something easy to understand for a practitioner”– Non-evidence summary user 7“Decision-makers noted the preference for a one-line sentence at the beginning of the evidence summary that provides a quick, clear, simple plain language indication of what the summary is based on with one decision-maker stating:“Can the key findings be presented in a graph or in an infographic instead of it being in word text format because it will be better visually and easier to digest”– Evidence summary user 1In addition to presenting the key findings from the full review, some decision-makers noted the need for background information related to the specific crisis. When we showed participants an example of an evidence summary retrieved from Evidence Aid website to solicit their feedback on it, they were not in favor of a text heavy summary. Instead, participants indicated their preference for key findings to be presented in a check list, bullet points, graph, or infographic format with one decision-maker stating:The infographic needs to capture the key findings from the research and include the key recommendations to me as a decision-maker. Those are the most critical information to go in the infographic”– Evidence summary user 1“Some decision-makers preferred to have key findings from the full review presented in infographics: stated in an interview preference for infographics to present the key findings from the full review:In the case of emergency management, time really matters, and infographics can get us (decision-makers) evidence in a quick format. They are also great because we can convert them into something that can be then consumed by the public. We can push them out through our social media or a press conference because they are easily consumed by the public”– Evidence summary user 4“A decision-maker noted that an additional benefit to using infographics is that they can be easily converted into a social media post to disseminate knowledge to the public stating:I would like to see a section in the summary about what we don’t know about it in terms of evidence or where there is no evidence available yet so that when somebody asks me the question of whether we (decision-makers) should be concerned about this? I can respond to them and say that there’s currently no evidence that shows that for example COVID-19 can be transmitted on surfaces”– Evidence summary user 4“Decision-makers also noted the importance of highlighting areas of uncertainty in the evidence or where evidence currently does not exist. A decision-maker stated:Research methods are only important to researchers but when it comes to translating the evidence to action, it is not as relevant”– Evidence summary user 2 while others noted “research methods provide an indication of how valid and reliable the results are and that’s why it is important to me” - Evidence summary user 7“The preference to indicate the research methods  from the full review as part of the findings section of the evidence summary yielded mixed results. Some decision-makers noted that:Most of my colleagues probably wouldn’t even understand the research methods employed by the full review because they do not have that kind of training, so it is a challenge to actually get some value out of that”– Evidence summary user 3“A decision-maker we interviewed that worked directly in COVID-19 response highlighted:“I need to know the fact  but I also want the implementation considerations highlighted so that if I need to take immediate action, I can do that. For example, with COVID-19 we needed not only needed to know the key actions to take in terms of social distancing, face masks and washing hands but we also needed to know how to implement such interventions to determine if it is feasible or not”– Evidence summary user 1Participants noted the need for implementation considerations to be explicitly stated and directly linked to the key findings presented with a decision-maker stating:“Contextual factors matter to me because when I am in the middle of project implementation in the field or designing for new projects, I need to know what contextual factors I need to keep in mind otherwise my projects will not be successful. I need to know if the evidence presented is applicable in low- and middle- income countries”– Non-evidence summary user 8Contextual implementation consideration emerged as a key theme in all our interviews. Decision-makers repeatedly noted the importance of having an explicit section in the evidence summary that highlights specific contextual information that decision-makers need to keep in mind when making decisions. A suggestion proposed by a decision-maker to capture contextual elements in the evidence summary is to include the list of countries or region that the evidence summary is focused on. Participants highlighted this by stating:Assessment of the quality of evidence is very useful, especially if you wanted to use it for programmatic development or as justification for what you want to do”– Evidence summary user 1“Decision-makers noted the importance of having a neutral entity assessing the quality of the evidence presented with one decision-maker stating:do not have the time to validate the sources, and this is why I prefer summaries that assess the quality of evidence presented” – Non-evidence summary user 9.Another decision-maker noted that because time is limited when operating in crises zones, they “It is important to know where the sources are coming from and this is why citation is key, we want to see if this is a legitimate research study coming from a credible site”– Evidence summary user 4“Decision-makers highlighted that having the full citation of the systematic reviews and other forms of evidence synthesis allows them to assess whether the source is one they can trust but gave it little preference in terms of order of appearance in the summary, with one decision-maker noting:A request has to be sent to the Librarian at the organization which could take three to four days for a response and the reality is that in some countries that we operate in a Librarian is not available to help us access full reviews”– Non-evidence summary user 10“Access to the full review the summary was written from was noted as an important feature in evidence summaries. A senior decision-maker noted that sometimes to access the full review:As a practitioner working in the field, I am probably not going to pull the full review or look for additional information as opposed to someone working in preparedness or mitigation efforts where they might have more time and are not operating in a time-sensitive context. The full review and additional information are more for planning purposes and not in the acute phases of disaster response”– Evidence summary user 3“Decision-makers highlighted the need to have the full review hyperlinked within the evidence summary for easier access. They also noted the need for hyperlinks to additional information on the topic to be inserted at the end of the evidence summary along with tagging of key words. Decision-makers noted that the desire to access the full review or further information on the topic is dependent on what phase of the emergency response they are in with one decision-maker stating:I would want to see where the authors received funding to conduct the research to determine credibility of the evidence presented and if there are any obvious conflicts of interests”– Non-evidence summary user 11“Indicating the funding source behind the full-review was noted as a preference by decision-makers to determine if there are any conflict of interests present in the findings presented in the evidence summary with one decision-maker noting:I think the shorter, the better, especially when we are talking about non-researchers who want the evidence in the most succinct way possible. Half a page will be enough but definitely not more than one-page”– 6 Evidence summary user“Decision-makers consistently stated that they preferred of having a one-page summary of the evidence with a senior decision-maker highlighting this in their remarks:Our study provided a further information of the preferences of decision-makers working in health and humanitarian crises for the format of evidence summaries to enable real-time evidence informed decision-making. In situations where time or resources are limited, evidence summaries take precedence in informing decision-making over extensive systematic reviews. Short summaries with key actionable messages highlighted in a bullet point format or infographics are strongly preferred. The use of infographics and graphs are strongly preferred to visually illustrate the findings. Infographics are an effective way to present complex and rapidly available information in a visually appealing format and is considered directly useful for decision-making purposes , 4. TheyThis study emphasizes that decision-makers working in crises prefer curated information sources  and to access websites that are easy to use . The reliance on those two specific sources of information is a result of the time-pressured situations decision-makers working in crises are under. They are expected to make decisions in a short time frame, often with limited information to inform their decisions. In-house technical advisors can provide evidence to decision-makers in a format they can easily understand, trust, and act upon in real-time. The preference for contextualized evidence summaries also emerged as a key finding. This is understandable given that contextual factors may have an impact on the health equity of an intervention, the feasibility of implementing an intervention, and the acceptability of an intervention . IncludiThe study identified the following challenges decision-makers face when trying to find and use research evidence in crises: insufficient time and increased burden of responsibilities during crises, limited access to reliable internet connection, burden of navigating websites, a large volume of data not translated into user friendly summaries, a plethora of different websites on the same topic, and little information available on preparedness and response measures. These different challenges provide insight into potential areas of improvement that knowledge producers working at addressing the knowledge needs of decision-makers working in crises can consider. Stakeholders working in health and humanitarian emergencies have specific knowledge needs and these findings reaffirm the importance of conducting further scholarly work that focuses on better understanding on how to best support evidence use in crises.Our findings that evidence summaries for ‘real-time’ evidence informed decision-making in crises are likely easier to understand than complete systematic reviews align with other published studies that examined the effectiveness of evidence summaries on health policymakers and health systems managers , 29–31. There are three strengths to this study. This is the first study to address the knowledge gap in our understanding of decision-making experiences with rapid evidence summaries to support real-time evidence informed decision-making in crises. Second, this study was strengthened by our mixed-method approach of incorporating surveys and interviews. Survey results gave an overview of attitudes and preferences of decision-makers using evidence summaries. The interviews illuminated survey responses by allowing us to further explore preferences and issues of participants. Overall, this approach enhanced the format of evidence summaries to support ‘real-time’ use of evidence in decision-making in crises. Third, we interviewed diverse types of stakeholders working in health and humanitarian emergencies encompassing various organizational affiliations to arrive at a comprehensive understanding of the preferred evidence summary template conducive for real-time evidence informed decision-making.One challenge to this study is that although we aimed to have the same preference questions for both users and non-users of evidence summaries, non-users were not as familiar with evidence summary websites which required us to slightly adapt their preferences questions thereby limiting our ability to compare some of the preferred features between the two groups. To address this challenge, we presented evidence summary websites to non-users during our follow up interviews to gather their preferred features.Writing summaries in a clear, succinct, and action-oriented format .Identifying the target audience the summary is intended for.Highlighting the most up-to-date evidence on fast emerging crises where evidence might be lacking and/or is continuously undergoing updating .Standardizing the format of evidence summaries to make it easier for them to read it quickly in real-time.Presenting the contents of evidence summaries in alternate formats . This will help in addressing the time limitation decision-makers face in the midst of a health and humanitarian emergency.Emphasizing the role of organizational stewardship in ensuring that decision-makers have free access to evidence summaries but also dedicated time to read them to inform their decision-making.Our findings suggest six ways to improve the synthesis of evidence summaries to allow real-time evidence informed decision-making in crises:The results of our study carry with them some implications in health and humanitarian emergency response. With the right knowledge management systems in place; our evidence summary template can streamline the process of responding to decision-makers knowledge needs during a crisis. In addition, training workshops geared at researchers tasked with synthesizing evidence summaries will be necessary to ensure understanding and compliance with the evidence summary template. Lastly, organizations tasked with synthesizing evidence summaries related to health and humanitarian emergencies can use our practical recommendations to improve the structure of evidence summary websites and summaries. They could also continue to solicit feedback from the users of evidence summaries to ensure that evidence websites and summaries best meet their knowledge needs.The next steps in research could be for researchers to explore stakeholders’ experience with using our proposed evidence summary template to test if this format has improved the use of research evidence in ‘real-time’ evidence informed practice. Additionally, researchers could conduct a user-testing study to evaluate stakeholders experience with using infographics to inform decision-making. Specifically, they can explore the format and style of infographics preferred by decision-maker working in health and humanitarian emergencies.Overall, our participants view plain language rapid evidence summaries as a helpful tool to inform real-time decision-making in crises. This study summarized the key elements stakeholders working in health and humanitarian emergencies prefer in evidence summaries and provided an evidence summary template that can be used by organizations or individuals tasked with synthesizing evidence summaries to inform decision-making.Additional file 1: Figure 1. Example of an application of the evidence summary template to a real-world crisis. Table 1. Demographics/ Participants’background. Table 2. Preferences for Users. Table 3. Preferences for Non-Users.


Hyalomma are of concern, as these ticks are believed to be vectors of many pathogens responsible for human and animal diseases. However, we have observed that for many pathogens there are no vector competence experiments, and that the level of evidence provided by the scientific literature is often not sufficient to validate the transmission of a specific pathogen by a specific Hyalomma species. We therefore carried out a bibliographical study to collate the validation evidence for the transmission of parasitic, viral, or bacterial pathogens by Hyalomma spp. ticks. Our results show that there are very few validated cases of pathogen transmission by Hyalomma tick species.Current and likely future changes in the geographic distribution of ticks belonging to the genus  Borrelia burgdorferi sensu lato ”  with the Boolean operator “AND” in the PubMed and Scopus databases without date restriction. The literature search was conducted in English. We retained peer-reviewed research articles and reviews (not including conference proceedings) and book sections. Screening was conducted first on titles, then on abstracts, and finally on the full text when available. After reading the entire articles, the ones that were eliminated corresponded to those that did not have available data or no original data. The number of references found in each of the two databases is shown in Numerous pathogens—parasitic, viral, or bacterial—have been reported in the scientific literature as transmitted or potentially transmitted by ticks of the genus Hyalomma. The synthesis of these studies, with an attributed level of evidence of vectorial transmission, is reported in H. dromedarii, H. impeltatum, H. marginatum, H. rufipes, and H. truncatum.Crimean–Congo Hemorrhagic Fever Virus (CCHFv) by H. dromedarii.African Horse Sickness virus by H. truncatum.Venezuelan equine encephalitis virus by Theileria annulata by H. anatolicum, H. dromedarii, H. excavatum, H. lusitanicum, and H. scupense.Theileria equi by H. anatolicum and H. excavatum.Theileria lestoquardi by H. anatolicum.Theileria ovis by H. anatolicum.Babesia occultans by H. rufipes.Coxiella burnetii by H. aegyptium.Anaplasma marginale by H. excavatum.Rickettsia aeschlimannii by H. marginatum and H. rufipes.In conclusion, we observed that there are many missing pathogen vector competence experiments, and that the level of evidence provided by the scientific literature is often not sufficient to validate the existence of vectorial transmission. We conclude that the pathogen/tick associations for which transmission from an infected host to an initially healthy host via tick bite has been experimentally validated are the following: