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Purpose: Although smoking has not been associated with overall ovarian cancer risk, adifferent impact on various histotypes has been reported. Our aim is to provide an accurate, up-to-date estimate of the dose–risk relationships between cigarette smoking and epithelial ovarian cancer, overall and by histotypes. Methods: Using an innovative approach for the identification of original study publications, we conducted a systematic review and meta-analysis of epidemiological studies published on the topic until September 2018. Summary relative risks (RR) for cigarette smoking were estimated using random-effects models; dose–risk relationships were evaluated using one-stage random-effects models with restricted cubic splines. Results: Thirty-seven studies were considered in the meta-analysis. The summary RRs for current versus never smokers were 1.05 (95% confidence interval CI 0.95–1.16) for overall ovarian cancer, 1.78 (95% CI 1.52–2.07) for mucinous, 0.77 (95% CI 0.65–0.93) for clear cell, 0.81 (95% CI 0.73–0.91) for endometrioid, and 1.05 (95% CI 0.94; 1.17) for serous cancer. The risk of borderline mucinous (RR 2.09) and serous (RR 1.16) tumors was higher than for invasive cancers (RR 1.44 and 0.95, respectively). For mucinous cancer, risk was noticeably higher with smoking intensity and duration (RR 2.35 for 20 cigarettes/day, and 2.11 for 20years of smoking). A non-significant linear relation was found with smoking intensity, duration, and time since quitting for overall ovarian cancer and other histotypes. Conclusions: This uniquely large and comprehensive meta-analysis confirms that although cigarette smoking does not appear to be a risk factor for ovarian cancer, andit is even slightly protective for some rare histotypes, there is a strong dose–risk relationship with mucinous ovarian cancer.

Background The hazard ratio (HR) is the most common measure used to quantify treatment effects in heart failure (HF) clinical trials. However, the HR is only valid when the proportional hazards assumption is plausible, and the HR may be difficult to interpret for clinicians and laypeople. Restricted mean survival time (RMST), defined as the average time-to-event before a specific timepoint, is an intuitive summary of group-wise survival. The difference between two RMSTs measures treatment effects without model assumptions and may communicate more clinically interpretable results. Purpose To evaluate statistical and clinical properties of RMST-based statistics applied to clinical trial data for treatments of HF with reduced ejection fraction. Methods Patient time-to-event data was reconstructed from the published primary and secondary outcome Kaplan-Meier curves from landmark HF clinical trials. We estimated the RMST-differences between treatment groups as a measure of treatment effect with published data, and compared statistical testing results and effect size values to HR analysis results. Results We analyzed 7 HF clinical trials, including data from a total of 27,845 patients (Table 1). RMST should be interpreted as the average number of months that the outcome is avoided over the study period. As examples: On average, treatment with enalapril for 12 months extended each patient's life by 2.2 months compared to placebo, and treatment with spironolactone for 34 months extended each patient's life by 2.2 months compared to placebo. Conclusions RMST-difference test statistic has identical statistical conclusions as HRs but provided an intuitive estimate of each treatment effect. RMST-based data can potentially be used to better communicate treatment effects to patients, to assist in patient-preference discussions and shared decision-making Funding Acknowledgement Type of funding source: None

Diverticular disease is a common disorder. Several guidelines report on its optimal management. The aim of this study was to describe the evolution of the prevalence of this disease, the treatment strategies, and the mortality rate on a national level.We conducted a retrospective study on prospective data using a nationwide database. All consecutive adult patients diagnosed with diverticular disease and admitted via the emergency department from 2009 to 2018 were included in the study. We performed a descriptive analysis for epidemiologic data, diagnosis, and treatment.During the data collection period, 233,386 patients were included in the study. The number of admissions for emergent diverticular disease increased by 65.8%, from 16,754 in 2009 to 27,781 in 2018, for both uncomplicated and complicated diverticular disease. Among these patients, 19,350 (8.3%) were operated on. The rate of surgical treatment progressively decreased from 9.7% in 2009 to 7.6% in 2018. The three main interventions were Hartmann's procedure (HP, n = 9111, 47.1%), resection with primary anastomosis (RPA, n = 4335, 22.4%), and peritoneal lavage (PL, n = 4836, 25%). We observed a progressive annual increase in HPs (n = 716 in 2009 and n = 1055 in 2018) as well as a decline in PLs since 2015, while the number of RPAs remained stable.Although admissions for emergent diverticular disease have increased during the study period, the rate of surgical treatment has decreased, suggesting an evolution toward more conservative management of this pathology.

Women's role in agriculture is widely reported to be essential; despite this, women's role in the wheat-sector is under-researched. Feminist standpoint theory is applied in analyzing 73 documents on women's role in agriculture from 1990 until 2016 to answer the following questions: How does the world look, and operate, for males and females in wheat growing households? What do we know about social relationships and mediating processes (i.e., social factors mediating men's and women's access to resources and activities) that exist in the prime wheat growing regions in Pakistan? The paper highlights a knowledge gap in relation to the life histories, local experiences, as well as unofficial and informal networks of small farmers in general, and of poor and marginalized women in particular. This neglect of rural subjects is a missed opportunity to learn and to engage in improved program design that contributes to enhanced food security and resilience in rural communities. The paper is relevant to development professionals and agriculture researchers and proposes further research questions on topics that appear to have an influence on women's role in wheat farming and food systems and women's ability to be successful in securing a wheat-based livelihood.

Aim Cigarette smoking is an established risk factor for pancreatic cancer but an updated quantification of the association is lacking. Our aim is to provide the most accurate and updated estimate of the dose–response relationships between cigarette smoking and pancreatic cancer risk. Methods Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of epidemiological studies published on the issue up to April 2017. Random effects models were used to provide pooled estimates for the cigarette smoking status; dose–risk relationships were evaluated using one-stage random effects models with restricted cubic splines. Results Seventy-eight studies were included, providing a pooled relative risk (RR) of pancreatic cancer of 1.8 (95% confidence interval, CI: 1.7–1.9) for the current and 1.2 (95% CI: 1.1–1.2) for the former vs. never smokers. A sharp increase in pancreatic cancer risk was found already with a low number of cigarettes and up to 30 cigarettes/day (RR 2.2, 95% CI: 1.9–2.4). Similarly, the risk of pancreatic cancer steady increased after a few years of smoking up to 30 years (RR 1.8, 95% CI: 1.6–2.0). The risk rapidly decreased with increasing time since quitting and was 0.6 (95% CI: 0.5–0.7, for the former vs. current smokers) after 20 years of quitting. Conclusions The present meta-analysis indicates that pancreatic cancer risk sharply increases with a low number of cigarettes or after a few years of smoking and that it rapidly decreases a few years after cessation, although it takes almost 20 years to reach that of never smokers.

Background Omalizumab therapy is effective and safe in patients with chronic spontaneous urticaria (CSU) resistant to nonsedating histamine 1 (H 1 ) antihistamines (nsAHs). Objective To evaluate the efficacy and safety of omalizumab in elderly (aged ≥65 years) patients with nonsedating H 1 -antihistamine–refractory CSU in a real-life setting. Methods Patients with nonsedating H 1 -antihistamine–refractory CSU (n = 322) treated with omalizumab administered every 4 weeks in doses of 300 mg for 24 weeks were divided into 2 groups according to age at omalizumab treatment onset: 15 to 64 years and 65 years or older. Treatment response was assessed using a 7-day urticaria activity score (UAS7). Adverse effects of omalizumab therapy were recorded. Results Among patients, 32 (9.9%) were 65 years or older. At baseline, CSU characteristics were generally similar among the groups, although the presence of angioedema was statistically significantly lower in patients younger than 65 years. Any differences in weekly itch severity score, hive score, and UAS7 between the 2 age groups were not significant at weeks 4, 12, and 24, with the exception of the hive score at 24 weeks and the UAS7 at week 24. No significant between-group differences were seen in the proportion of patients with a UAS7 of 6 or lower and with a UAS7 score of 0 at weeks 4, 12, 24, and 40. The proportion of patients with at least one adverse event reported as suspected to be caused by study drug was 10% in the younger group vs 6.3% in the older group ( P = .53). Conclusion Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with nonsedating H 1 -antihistamine–refractory CSU.

Il n’existe jamais une absolue coïncidence entre les conceptions, les valeurs et les normes du monde de la justice et celles de la société. Ce sont les écarts, les distances ou les proximités entre les conceptions de l’une et l’autre que ce livre entreprend d’explorer dans le temps. Au haut Moyen Âge, des évêques ferment les yeux sur des infractions à la législation sur le mariage ; au XIVe siècle, l’application rigoureuse de la législation relative à l’endettement rompt le lien social ; dans l’Italie du Nord, des pratiques coutumières sont utilisées par les tribunaux du pape pour accuser d’hérésie de grands seigneurs ; dans les états bourguignons, les dispositions brutales de la justice ducale brisent des solidarités urbaines fortes ; aux XVe-XVIe siècles, la pratique de l’homicide pour adultère trouve dans la société un quasi consensus ; en 1720, une large partie de l’opinion publique réprouve la sévérité à l’encontre d’un bandit… Parallèlement apparaissent des proximités et des convergences, comme au XIIe siècle dans l’Italie des communes. Au XVIIIe siècle, des tribunaux de proximité renvoient l’image d’une communauté de valeurs entre juges et justiciables. Dans le jugement des blasphèmes, les juges se gardent d’appliquer à la lettre la législation pénale, du moins jusqu’à la fin du XVe siècle, tandis que la mutation provoquée par la Réforme protestante suggère que l’analyse en termes de tolérance est inappropriée pour en rendre compte. Ce que l’on découvre au fil des analyses, c’est une distance entre les valeurs partagées par la société et certaines pratiques judiciaires étroitement liées au pouvoir politique, le pouvoir souverain, soit en expansion, soit, au contraire, en difficulté. Ce livre éclaire donc aussi, à côté de la force de la justice négociée et de la proximité qu’elle maintient entre magistrats et justiciables, l’ambivalence de la justice en tant qu’attribut de la souveraineté.

Longtemps mineure parmi les interrogations des historiens de la justice d’Ancien Régime, la question du jugement porté par la population sur l’exercice du droit de punir fait aujourd’hui partie intégrante de ce champ de recherche grâce, pour la France, aux travaux de Pascal Bastien sur les exécutions publiques dans le Paris du XVIIIe siècle. De fait, pour les pénalistes de l’ancienne France, une part importante du principe actif des châtiments reposait sur la présence d’une foule de spectateu...

Introduction Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. Methods and analysis To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics and dissemination Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking. Trial registration number This protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991).

Kounis syndrome is defined as the co-incidental occurrence of an acute coronary syndrome with hypersensitivity reactions following an allergenic event and was first described by Kounis and Zavras in 1991 as an allergic angina syndrome. Multiple causes have been described and most of the data in the literature are derived from the description of clinical cases - mostly in adult patients - and the pathophysiology remains only partly explained. Three different variants of Kounis syndrome have been defined: type I (without coronary disease) is defined as chest pain during an acute allergic reaction in patients without risk factors or coronary lesions in which the allergic event induces coronary spasm that electrocardiographic changes secondary to ischemia; type II (with coronary disease) includes patients with pre-existing atheromatous disease, either previously quiescent or symptomatic, in whom acute hypersensitive reactions cause plaque erosion or rupture, culminating in acute myocardial infarction; more recently a type-III variant of Kounis syndrome has been defined in patients with preexisting coronary disease and drug eluting coronary stent thrombosis. The pathogenesis of the syndrome is discussed, and a therapeutic algorithm is proposed.

Introduction Treatment effects in heart failure (HF) clinical trials are typically summarized as hazard ratios (HR). However, a HR alone without a reference value of the hazard from the control arm is difficult to interpret and is valid only when hazards are proportional throughout the trial. The restricted mean survival time (RMST) describes the mean time free from an event and does not require any model assumption. Comparison of RMSTs between treatment and control arms, either by differences or ratios, is a more intuitive summary of treatment effects than HR. Objective Compare RMST with HR in HF device clinical trials. Methods Time-to-event data was reconstructed from published Kaplan-Meier curves from landmark HF trials. We calculated the RMST-differences and restricted mean time loss (RMTL) ratios between treatment groups as measures of treatment effect, and compared statistical testing results to HR. Results We analyzed 4 clinical trials with a total of 5,186 patients. Statistical significance tests were concordant between HR and RMST or RMTL for all outcomes (Table 1). However, RMST analyses provided additional clinically useful information: for instance, in COAPT, percutaneous mitral valve repair extended each patient's life 1.7 months on average compared to medical therapy alone, over 2 years follow up. In MADIT II, implantable cardioverter defibrillator (ICD) implantation extended each patient's life on average by 2.9 months compared to medical therapy, over the 4 years of the trial, and in MADIT-CRT, cardiac resynchronization therapy added on average 3.2 months to each patient's life compared to ICD alone, over 4 years of follow up. Conclusions RMST achieved similar statistical testing results as HR but provides an intuitive estimate of treatment effect. RMST-based analysis may better communicate treatment effects to patients, to assist in patient-preference discussions and shared decision-making.

Background Component resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenic source, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy. Objective The aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient's overall management according to the two different approaches. Methods An overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness. Results An approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected. Conclusion There is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach.

There is a need for validated tools to assess health-related quality of life (HRQoL) in routine clinical practice.The aim of this study was to validate the Chronic Urticaria Patient Perspective (CUPP) for assessment of patients with chronic urticaria (CU) in clinical practice.A provisional CUPP was developed from candidate items identified by following an iterative process in a retrospective analysis of 249 Chronic Urticaria Quality of Life Questionnaire questionnaires. The psychometric properties of the CUPP were then tested on a sample of patients enrolled in 13 Italian centers.The study population in the validation phase comprised 152 patients. The 10-item version of the CUPP showed satisfactory internal consistency (Cronbach's alpha values of 0.76 at visit 1 and 0.90 at visit 2), good criteria, and discriminative and convergent validity. Reliability was assessed in 34 patients with no changes in health (Global Rating Scale = 0 at visit 2) and was satisfactory (CCC [concordance correlation coefficient] = 0.9). Changes in CUPP scores were significantly associated with changes in Urticaria Activity Score (UAS)-Hive count (r = 0.36, P .001), UAS-Itch severity (r = 0.48, P.001), and UAS-Total score (r = 0.342, P.001), all of which indicated good responsiveness. The minimal important difference was 1.5.CUPP is a simple 10-question tool with good psychometric properties that provides a valid, reliable, and standardized measurement of HRQoL in patients with CU.

Mentre Adanech mi mostra la sua scorta di kosso (Hagenia abyssinica) – solo i fiori femminili, essiccati e pestati, entrano nell’infuso - ripete che non ha paura del dolore. Come altre donne in zona Hadiya, nonostante la pianta sia stata bandita per la sua tossicità dalle politiche di salute pubblica, ne usa dosi sapienti per purgarsi in tempi ordinari e rafforzarsi in gravidanza. Così, prosciugando il corpo, eliminando le eccedenze e attraverso una disciplina dello stomaco che scalda e purifica, si producono secondo ricette locali bambini ben formati e donne di grande valore. Ed è attraverso la manipolazione dei corpi che queste testimoni ci offrono un’interpretazione inedita del concetto di persona e dei nessi fra cibo e potere.