Sicily

西西里岛
  • 文章类型: Journal Article
    背景:流感是一种严重的公共卫生威胁,特别是对于严重病例和疾病并发症的管理,要求实施控制措施。我们旨在评估在巴勒莫地方卫生局(LHA)运营的家庭儿科医生(FPs)代表性样本中qLAIV疫苗接种的接受度和影响。为此,我们评估了疫苗接种率,将其与西西里背景下观察到的进行比较,同时积极监测可能的不良反应及其严重程度。
    方法:一项观察性描述性非对照研究分两个阶段进行,从2022年9月到2023年6月。第一阶段包括形成性和教育性干预,并提供干预前问卷,以评估FPs对小儿流感疫苗接种的知识和态度。第二阶段包括积极监测qLAIV安全性和在参与的FP协助下的儿科人群的接受度,从2022年10月到2023年4月。频率,卡方检验,使用Stata/MP14.1进行比较统计。
    结果:参与干预的儿科人群的总体覆盖率为13.2%,施用的疫苗的I.M./qLAIV比率为1/4.25。与巴勒莫地方卫生局(LHA)(6.7%)和整个西西里岛(5.9%)的人口报告的平均值相比,该覆盖率明显更高(p值<0.001)。qLAIV组的不良事件为轻度,只有3.3%的人经历过,主要表现为发烧上升(3.2%)。无严重不良反应报告。
    结论:教育干预显著提高了参与项目的儿童流感疫苗接种率,总体上提高了巴勒莫LHU的流感疫苗接种率。最小,非严重不良事件强调了疫苗的安全性。培训课程确保儿科医生保持知情,使他们能够向父母提供全面的信息,以便在他们的实践中做出安全和明智的疫苗接种决定。
    BACKGROUND: Influenza represents a serious public health threat, especially for the management of severe cases and complications of the disease, requiring the implementation of control measures. We aimed to assess the acceptance and impact of qLAIV vaccination among a representative sample of family paediatricians (FPs) operating in Palermo Local Health Authority (LHA). To this end we evaluated vaccination coverage rates, comparing it with that observed in Sicilian context, while actively monitoring possible adverse reactions and their severity.
    METHODS: An observational descriptive non-controlled study was conducted in two phases, from September 2022 to June 2023. The first phase involved a formative and educational intervention with a pre-intervention questionnaire to assess the knowledge and attitudes of FPs on paediatric influenza vaccination. The second phase consisted of an active surveillance on qLAIV safety and acceptance among the paediatric population assisted by the participating FPs, from October 2022 to April 2023. Frequencies, chi-squared tests, and comparisons statistics were performed using Stata/MP 14.1.
    RESULTS: The overall coverage rate among the paediatric population involved in the intervention was 13.2%, with an I.M./qLAIV ratio of vaccine administered of 1/4.25. This coverage rate was significantly higher (p-value <0.001) when compared to the average values reported in the population under the Palermo Local Health Authority (LHA) (6.7%) and in the entire Sicily (5.9%). Adverse events in the qLAIV group were mild, with only 3.3% experiencing them, primarily presenting as a feverish rise (3.2%). No severe adverse reaction was reported.
    CONCLUSIONS: The educational intervention significantly raised paediatric influenza vaccination rates among the participating FPs, and in general improved influenza vaccination coverage rates in the Palermo\'s LHU. Minimal, non-serious adverse events underscored the vaccine\'s safety. Training sessions ensured paediatricians stayed informed, enabling them to provide comprehensive information to parents for secure and informed vaccination decisions in their practices.
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  • 文章类型: Journal Article
    人类的健康,动物和环境是相互联系的。采取“一个健康”的方法意味着及时干预以预防影响动物健康的主要疾病,以确保畜牧业生产安全。绵羊暴露于有毒微量元素会导致在不同生物基质中的积累增加,在人类和牲畜中发展急性和慢性疾病。这项研究的目的是评估砷(As)的生物积累,镉(Cd),使用以下生物底物在西西里巴黎斯卡绵羊中的铅(Pb)和汞(Hg):牛奶,血和羊毛.电感耦合等离子体质谱仪(ICP-MS)用于As,Cd和Pb,直接汞分析仪(DMA-80)用于汞的测定。此外,评估了血液学参数作为不同生物分布的可能指标的作用.从我们分析的基材中的金属中观察到统计学上的显着值:砷(p<0.001),镉(p<0.01),铅(p<0.001)和汞(p<0.0001)。相关性分析显示牛奶和血液中砷(p<0.0001)和铅(p<0.0001)的关系,并且在本研究中观察到的低浓度安慰最终消费者的血液/血液与分析的血液学参数之间没有观察到金属的相关性。
    The health of humans, animals and the environment is interconnected. Adopting a One Health approach means intervening promptly to prevent the main diseases that affect animal health to guarantee the safety of livestock production. Exposure to toxic trace elements in sheep can lead to increased accumulation in different biological substrate, developing both acute and chronic diseases in humans and livestock. The aim of this study was to evaluate the bioaccumulation of arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) in Sicilian Barbaresca sheep using the following biological substrates: milk, blood and fleece. An inductively coupled plasma mass spectrometer (ICP-MS) was used for As, Cd and Pb, and a direct mercury analyser (DMA-80) was used for Hg determination. In addition, the role of the haematological parameters as possible indicators of different biodistribution was evaluated. A statistically significant value was observed from our analysed metals in the substrates: arsenic (p < 0.001), cadmium (p < 0.01), lead (p < 0.001) and mercury (p < 0.0001). The correlation analysis showed a relationship between milk and blood for arsenic (p < 0.0001) and lead (p < 0.0001), and no correlation for the metals was observed between milk/blood and the haematological parameters analysed for the low concentration observed in the present study comforting the final consumer.
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  • 文章类型: Journal Article
    在这项研究之前,没有与Cirnecodell\'Etna品种的生殖生理有关的数据。在意大利养犬俱乐部国家机构(ENCI)注册的141只母狗和104只父亲的出生日期,来自所有西西里育种者,以及与它们肥沃的交配有关的数据,在14年的时间里生产了266只幼崽,(2009-2022)被收集。总共幼崽产生了1069只幼崽。初生时的平均母狗年龄为39.13±21.7个月,平均产仔数为3.84±2.08。母猪和母猪的出生时期受一年中月份的影响显着(p<0.01),第一个(p<0.05)和随后的产卵期(p<0.01)的分布也是如此。Whelping分布显示,4月的最高峰(大致对应于2月的发热量)和7月的最高峰(大致对应于5月的发热量)与3月的最低峰之间存在显着差异。未发现月份对产仔数和性别比的影响。现有数据表明,一些古老的品种,如Cirnecodell\'Etna,可能显示出季节性模式,作为其最接近狼的严格季节性的痕迹。
    Previous to this study, there is no data relating to the reproductive physiology of the Cirneco dell\'Etna breed. The birth date of 141 bitches and 104 sires registered at the National Agency of the Italian Kennel Club (ENCI) from all Sicilian breeders, and data related their fertile matings, which produced 266 whelps over a 14-year period, (2009-2022) were collected. Total whelping produced 1069 pups. The mean bitch age at first whelping was 39.13 ± 21.7 months and the mean litter size was 3.84 ± 2.08. The birth period of the bitches and sires was significantly influenced by the month of the year (p < 0.01), as was the distribution of the first (p < 0.05) and subsequent whelping periods (p < 0.01). Whelping distributions show a significant difference between the highest peak in April (which roughly corresponds to a period of heat in February) and in July (which roughly corresponds to a period of heat in May) and the lowest peak in March. No influence of month on litter size and sex ratio was found. Available data suggests that some ancient breeds such as the Cirneco dell\'Etna may show seasonal patterns as a vestige of the stricter seasonality of its closest relative the wolf.
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  • 文章类型: Journal Article
    背景:再感染是由于对自然感染的反应减弱而发生的,并且出现了SARS-CoV-2的新型菌株。本研究探讨了性别之间的相关性,年龄,COVID-19疫苗接种,先前的感染住院治疗,和SARS-CoV-2在西西里岛再次感染,意大利。材料和方法:一项基于人群的回顾性队列研究使用了来自区域注册和意大利卫生研究所西西里COVID-19监测系统的疫苗接种通量进行了阐述。这项研究只包括成年西西里人,和风险比使用Cox回归计算。结果:部分疫苗接种提供了一定的保护(adj-HR:0.92),与未接种疫苗的个体相比;此外,完全接种疫苗降低了再感染风险(调整HR:0.43),和加强剂量(adj-HR:0.41)。男性再次感染SARS-CoV-2的风险低于女性(调整HR:0.75)。在首次感染期间住院减少了SARS-CoV-2的再感染(调整HR:0.78)。与18-29岁的人群相比,30-39岁和40-49岁的人群的再感染风险更高,而60-69岁、70-79岁和80岁以上的人群则受到统计学保护。在野生型Alpha期间,再感染明显更频繁,Delta,Delta-Omicron,和Omicron优势/共优势波与野生型相比。结论:本研究通过查明最紧迫的政策障碍并确定一些主要因素,为理解西西里岛的再感染现象奠定了坚实的基础。COVID-19疫苗接种,最有效的公共卫生工具之一,防止再感染,主要是由Omicron菌株引起的。老年人和住院患者的风险较低,建议使用更严格的PPE。
    Background: Reinfections occur as a response to natural infections wanes and novel strains of SARS-CoV-2 emerge. The present research explored the correlation between sex, age, COVID-19 vaccination, prior infection hospitalization, and SARS-CoV-2 reinfection in Sicily, Italy. Materials and Methods: A population-based retrospective cohort study was articulated using the vaccination flux from a regional registry and the Sicilian COVID-19 monitoring system of the Italian Institute of Health. Only adult Sicilians were included in the study, and hazard ratios were calculated using Cox regression. Results: Partial vaccination provided some protection (adj-HR: 0.92), when compared to unvaccinated individuals; furthermore, reinfection risk was reduced by full vaccination (adj-HR: 0.43), and the booster dose (adj-HR: 0.41). Males had a lower risk than females of reinfection with SARS-CoV-2 (adj-HR: 0.75). Reinfection with SARS-CoV-2 was diminished by hospitalization during the first infection (adj-HR: 0.78). Reinfection risk was higher among those aged 30-39 and 40-49 compared to those aged 18-29, whereas those aged 60-69, 70-79, and 80+ were statistically protected. Reinfection was significantly more frequent during the wild-type-Alpha, Delta, Delta-Omicron, and Omicron dominance/codominance waves compared to the wild type. Conclusions: This study establishes a solid base for comprehending the reinfection phenomenon in Sicily by pinpointing the most urgent policy hurdles and identifying some of the major factors. COVID-19 vaccination, one of the most effective public health tools, protects against reinfection, mostly caused by the Omicron strain. Elderly and hospitalized people\'s lower risk suggests stricter PPE use.
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  • 文章类型: Journal Article
    布鲁氏菌病是世界上主要的人畜共患病原体之一,在流行地区造成巨大的经济损失和相当大的人类发病率。人类布鲁氏菌病的明确控制需要通过易于应用于该领域的实用解决方案来控制牲畜中的布鲁氏菌病。在意大利,布鲁氏菌病仍然在南部几个省份流行,尤其是在西西里地区。本文的目的是描述已开发的布鲁氏菌病模型及其应用,试图尽可能忠实地再现布鲁氏菌病的复杂传播过程,说明放牧动物的混合。该模型着重于受污染的环境,而不是受感染的动物,使用西西里岛地区主要放牧区的真实数据,并旨在确定最佳控制方案,以最大程度地减少传播(和流行率)并在有关地区实现根除。模拟结果证实了早期应用控件的有效性,显示控制应在牧场后30天进行,剔除时间可以忽略不计。此外,结果强调了出生和放牧牧场的时间(及其相互作用)比其他因素更重要。由于这些因素是特定地区的,这项研究鼓励采用不同的和新的根除工具,调整每个地区的放牧和商业行为。本研究将进一步扩展以提高模型对现实世界的适应性,目的是使该模型成为能够帮助决策者加速在意大利根除布鲁氏菌病的操作工具。
    Brucellosis is one of the world\'s major zoonotic pathogens and is responsible for enormous economic losses as well as considerable human morbidity in endemic areas. Definitive control of human brucellosis requires control of brucellosis in livestock through practical solutions that can be easily applied to the field. In Italy, brucellosis remains endemic in several southern provinces, particularly in Sicily Region. The purpose of this paper is to describe the developed brucellosis model and its applications, trying to reproduce as faithfully as possible the complex transmission process of brucellosis accounting for the mixing of grazing animals. The model focuses on the contaminated environment rather than on the infected animal, uses real data from the main grazing areas of the Sicily Region, and aims to identify the best control options for minimizing the spread (and the prevalence) and to reach the eradication within the concerned areas. Simulation results confirmed the efficacy of an earlier application of the controls, showed the control should take place 30 days after going to pasture, and the culling time being negligible. Moreover, results highlighted the importance of the timing of both births and grazing pastures (and their interaction) more than other factors. As these factors are region‑specific, the study encourages the adoption of different and new eradication tools, tuned on the grazing and commercial behavior of each region. This study will be further extended to improve the model\'s adaptability to the real world, with the purpose of making the model an operational tool able to help decision makers in accelerating brucellosis eradication in Italy.
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  • 文章类型: Journal Article
    这项工作的目的是研究小芥子亚种。在西西里岛(意大利)自发生长的毛竹,是活性代谢物的新潜在来源;特别是,对叶子的比较研究,花,和茎水醇提取物进行。通过分光光度法定量测定多酚,并通过HPLC-PDA/ESI-MS进行表征;共鉴定出55种多酚化合物,突出了相当不同的定性-定量概况。提取物表现出抗氧化活性,通过体外试验评估;特别是,叶提取物表现出最佳的自由基清除活性(DPPH试验)和还原能力,而花提取物显示出最大的螯合活性。通过标准方法研究了提取物对细菌和酵母的抗微生物特性;未发现对测试菌株的抗微生物活性。通过卤虫致死性生物测定法进行初步毒性评估后,提取物结果无毒。毛竹亚种的地上部分。毛竹被证明是用于制药和营养食品应用的抗氧化剂的宝贵来源。
    This work aimed to investigate Sinapis pubescens subsp. pubescens spontaneously grown in Sicily (Italy) as new potential source of active metabolites; specifically, a comparative study on leaf, flower, and stem hydroalcoholic extracts was performed. Polyphenols were quantitatively determined by spectrophotometric methods and characterized by HPLC-PDA/ESI-MS; a total of 55 polyphenolic compounds were identified, highlighting considerably different qualitative-quantitative profiles. The extracts showed antioxidant activity, evaluated by in vitro assays; particularly, the leaf extract displayed the best radical scavenging activity (DPPH test) and reducing power, while the flower extract showed the greatest chelating activity. The antimicrobial properties of the extracts were investigated against bacteria and yeasts by standard methods; no antimicrobial activity was found against the strains tested. The extracts resulted to be non-toxic after preliminary toxicity evaluation by the Artemia salina lethality bioassay. The aerial parts of S. pubescens subsp. pubescens proved to be valuable sources of antioxidants for pharmaceutical and nutraceutical applications.
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  • 文章类型: Journal Article
    目前,在欧洲,大约五分之一的工人受雇于夜班工作。轮班工作,包括夜间时间是必不可少的几个活动,尤其是医疗保健部门。重要的是,夜间工作可能与睡眠障碍或工作相关压力的发生有关,两者都有可能增加工作中出错和事故的风险。这项研究旨在检查神经行为改变的存在,这可能是轮班工作以及睡眠时间和昼夜节律同时失调的结果。护士(n=102)受雇于位于西西里岛东北部的大学医院,意大利,自愿参加了这项试点研究。在医疗监视期间,早上和晚上收集唾液样本,并对所有受试者进行了7份心理诊断问卷。一方面,我们评估了应激相关生物标志物(皮质醇和α-淀粉酶)和昼夜节律生物标志物(褪黑素)的唾液水平.另一方面,评估了几种神经行为特征,包括抑郁症,焦虑,工作相关,和睡眠问题。有趣的是,唾液早晨皮质醇与抑郁量表呈正相关,以及唾液早晨α-淀粉酶和工作能力量表之间的负相关关系,被观察到。基于这些结果,主观问卷结果和客观唾液生物标志物量化的整合可以帮助识别更容易发生神经行为改变的工作者.这种方法可能有助于改善针对敏感类别的预防策略,如护士轮班工作。
    Currently, about one in five workers is employed in night shift work in Europe. Shift work including nighttime hours is essential in several activities, especially the healthcare sector. Importantly, night working may be associated with the occurrence of sleep disorders or work-related stress, both potentially augmenting the risk of errors and accidents at work. This study aims to examine the presence of neurobehavioral alterations that can be a consequence of shift working and concurrent misalignment of the sleep times and circadian rhythms. Nurses (n = 102) employed at a University Hospital located in North-Eastern Sicily, Italy, voluntarily participated in this pilot study. During medical surveillance, morning and evening salivary samples were collected, and seven psychodiagnostics questionnaires were administered to all the subjects. On one hand, the salivary levels of stress-related biomarkers (cortisol and alpha-amylase) and a circadian biomarker (melatonin) were evaluated. On the other hand, several neurobehavioral features were assessed, including depression, anxiety, work-related, and sleep issues. Interestingly, a positive relationship between salivary morning cortisol and depression scale, as well as a negative relationship between salivary morning alpha-amylase and work ability scale, were observed. Based on these results, the integration of subjective questionnaire outcomes and objective salivary biomarker quantification can help to identify workers with increased susceptibility to developing neurobehavioral alterations. This approach may contribute to ameliorating preventive strategies towards sensitive categories, such as nurses working rotation shifts.
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  • 文章类型: Journal Article
    背景:克拉屈滨片是治疗复发缓解型多发性硬化症(RRMS)的高效选择。
    目的:评估克拉屈滨在现实世界中的有效性。
    方法:这项前瞻性现实世界研究连续筛选了来自西西里岛(意大利)七个不同MS中心的所有RRMS患者,在2019年3月11日至2021年10月31日期间完成克拉屈滨片的2年疗程。有关扩展残疾状态量表(EDSS)的数据,复发,以前的治疗,收集不良事件(AE)和磁共振成像(MRI).先前接受过其他DMT治疗的患者在中度积极治疗(MAT)和高度积极治疗(HAT)患者中进一步分层。
    结果:共217名患者,(70%的妇女,平均年龄38.4±11.3岁),已注册。50名患者(23.0%)未接受治疗,167名(77%)从另一种疾病修饰疗法转换。经过第二年的治疗,约80%的患者无EDSS进展,88%的患者在T24时保持无复发,48%的患者无MRI活动。KaplanMeier分析显示MT和HAT在首次临床复发的时间方面存在显着差异(HR:2.43,IC1.02-5.76;p=0.04),第一个新的T1-钆增强病变的时间(HR:3.43,IC1.35-8.70;p=0.009)和MRI恶化的时间(HR:2.42,IC1.15-5.09;p=0.02)。
    结论:这项研究证实克拉屈滨是MS的有效治疗方法,特别是在初治患者和那些从MATs转换的患者中。
    BACKGROUND: Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS).
    OBJECTIVE: The study aims to evaluate the effectiveness of cladribine in a real-world setting.
    METHODS: This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11th March 2019 and 31st October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) and magnetic resonance imaging (MRI) were collected. Patients who were previously treated with other DMTs were further stratified into moderately active treatment (MAT) and highly active treatment (HAT) patients.
    RESULTS: A total of 217 patients (70% women, with a mean age of 38.4 ± 11.3 years) were enrolled. Fifty patients (23.0%) were naïve to treatment and 167 (77%) switched from other disease modifying therapies. After the second year of treatment, about 80% were EDSS progression free, 88% remained relapse-free at T24, and 48% of patients were MRI activity-free. Kaplan Meier analyses showed significant differences between MT and HAT in terms of time to first clinical relapse (HR: 2.43, IC 1.02- 5.76; p = 0.04), time to the first new T1-gadolinium enhancing lesion (HR: 3.43, IC 1.35-8.70; p = 0.009) and time to MRI worsening (HR: 2.42, IC 1.15-5.09; p = 0.02).
    CONCLUSIONS: This study confirmed that cladribine is an effective treatment for MS, particularly in naïve patients and those who have switched from MATs.
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  • 文章类型: Journal Article
    植物和动物的季节性周期驱动着农业系统中人类实践的关键时机,比如收获的最佳时间,种植,或修剪。在历史物候研究的框架内,我们尝试重建千年来的橄榄(OleaeuropaeaL.)物候。由于其非凡的长寿,橄榄树是过去的活生生的代表,体现了对生态行为的长期记忆。一个文化基石物种,油橄榄种植在生物多样性保护中发挥着越来越重要的作用,农村社区的生计及其在整个地中海地区根深蒂固的文化身份。通过从历史书面来源和口头传统中汇编传统物候知识,并将其用作人类生态实践与植物行为的季节性变化之间联系的历史生物指标,我们编制了覆盖过去2800年的橄榄树每月生态日历。作为一个案例研究,我们选择了一个特别的地方:西西里,它在地中海的独特地位,跨时空积累的生态文化形式的地貌和遗产。这样一个独特的生态日历提供了一个额外的案例研究,以探索植物行为和人类适应策略的交织以及文化多样性之间的相互作用。生态扰动和物候稳定性。所有这一切,反过来,可以为这些千年树木的当前和未来可持续管理提供信息。
    Seasonal cycles in plants and animals drive key timings of human practices in an agrosystem like the best time for harvest, planting, or pruning. Within the framework of historical phenological studies, we attempt a reconstruction of the olive (Olea europaea L.) phenology along millennia. Thanks to its extraordinary longevity, the olive tree is a living proxy from the past and embodies a still uncollected long-term memory of ecological behaviors. A cultural keystone species, olive cultivation has more and more played a crucial role for biodiversity conservation, livelihood of rural communities and their enrooted cultural identity in the whole Mediterranean. By compiling traditional phenological knowledge from historical written sources and oral traditions, and using it as historical bio-indicator of the linkage between human ecological practices and seasonal changes of plant behavior, we compiled a monthly ecological calendar of the olive tree covering the last ∼2800 years. As a case study, we chose a special place: Sicily, unique for its position in the Mediterranean, geomorphology and legacies in the form of cross-temporal accumulated eco-cultures. Such a sui generis ecological calendar provides an additional case study to explore the intertwining of plant behavior and human adaptation strategies and the interplay between cultural diversity, ecological disturbance and phenological stability. All of this, in turn, can inform action for the present and future sustainable management of these millennial trees.
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  • 文章类型: Journal Article
    个性化医疗是一种新的医疗模式,以及社会文化性别的概念,与生物性别相反,出现在几种医学方法中。这项探索性研究旨在调查西西里医生对性别和临床医学的了解。数据收集是基于发送给西西里岛(意大利)医疗委员会成员的在线调查。问卷包括9个有关性别医学的认识和态度及其在临床实践中的重要性的具体项目。8023名西西里医生收到了邀请电子邮件,只有496人做出了回应。关于性别医学知识,71.1%的参与者表示他们知道,而88.5%的人认为性别医学应该纳入培训项目。同样,高百分比(77.6%)希望在这个主题上保持最新。抽样的医生似乎理解性别医学原则的重要性,尽管他们在一些性别问题上的经验(即,急性心血管护理和戒烟策略中的性别差异较低(55.44%和21.57%,分别)。这项探索性研究的结果应鼓励面对当前卫生专业人员课程中的性别医学差距,并应在临床环境中实施性别和性别原则的过渡价值。
    Personalized medicine is a new paradigm in health care, and the concept of socio-cultural gender, as opposed to biological sex, emerged in several medical approaches. This exploratory study aimed to investigate the knowledge of sex and gender in clinical medicine among Sicilian physicians. Data collection was based on an online survey sent to the members of the Medical Councils of Sicily (Italy). The questionnaire included nine specific items about awareness and attitudes regarding gender medicine and its importance in clinical practice. 8023 Sicilian physicians received the solicitation e-mail and only 496 responded. Regarding the knowledge of gender medicine, 71.1% of participants stated that they know it, while 88.5% believe that gender medicine should be included in training programs. Similarly, a high percentage (77.6%) would like to keep up to date on this topic. Physicians sampled seem to understand the importance of gender medicine principles, although their experience of some gender issues (i.e., sex disparities in acute cardiovascular care and smoking cessation strategies) is low (55.44% and 21.57%, respectively). The results of this exploratory study should encourage facing the gender medicine gap in the current curricula of health professionals and should implement the transitional value of sex and gender principles in the clinical setting.
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