Consumption of Fruits, Vegetables and Bladder Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

We examined the association between fruit/vegetable consumption and bladder cancer (BC) risk in a systematic review and meta-analysis of prospective cohort studies stratifying results by gender, smoking status and geographical region. Eligible studies were sought in MEDLINE and EMBASE up to April 20, 2020. Random-effects (DerSimonian-Laird) models were implemented for the calculation of pooled relative risks (RRs) and 95% confidence intervals (CI). Fifteen eligible studies were identified (1,993,881 subjects, 11,097 BC cases). Vegetable consumption (pooled RR = 0.95, 95% CI: 0.87-1.04, n = 10) as well as combined fruit/vegetable consumption was not associated with BC risk. Regarding fruit intake, the overall protective trend did not reach significance (pooled RR = 0.91, 95%CI: 0.81-1.02, n = 11); we found however a significant association in East Asians. A trend toward a protective association with citrus fruit consumption was also noted (pooled RR = 0.83, 95%CI: 0.69-1.01, n = 6), once again with a significant effect in East Asians. Moreover, no association was found regarding the subgroups of leafy vegetables, dark green vegetables, and berries. Single studies pointed to a reduced BC risk in never smoking males consuming cruciferous vegetables and East Asians consuming yellow vegetables. In conclusion, our study reveals possible protective effects; larger studies are needed to investigate the emerging trends.

Gut microbiome and attention deficit/hyperactivity disorder: a systematic review.

BACKROUND: This systematic review aims to examine the associations between features of gut microbiome and Attention Deficit/Hyperactivity Disorder (ADHD) risk or severity in children, adolescents and young adults. METHODS: Eligible studies were identified in PubMed and Google Scholar databases until December 31, 2020. RESULTS: The search identified a total of 1197 items, of which 11 were included in this systematic review. The findings regarding alpha, beta diversity, bacterial phyla, orders and families were inconclusive. At the genus level an increased abundance of Odoribacter (two studies) and Eggerthella (two studies) was found in ADHD; on the contrary, decreased abundance of Faecalibacterium (three studies) was noted, whereas one study suggested its inverse association with ADHD severity and hyperactivity. One study indicated that Bacteroides species also correlated with levels of hyperactivity and impulsivity. At the species level, a lower abundance of Faecalibacterium prausnitzii, but higher of Odoribacter splanchnicus and Bacteroides uniformis was reported. CONCLUSIONS: This systematic review highlights associations between gut microbiome features and ADHD. Potential mechanisms differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines. IMPACT: The existence of correlations between features of gut microbiome and ADHD manifestation or its severity in children, adolescents and young adults. Associations between gut microbiome features and ADHD are highlighted. Potential mechanisms seem to differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines. As correlations between gut microbiome features and ADHD seem to exist, additional studies are needed for further investigation.

Cardiometabolic factors and risk of non-arteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis of the literature is to evaluate the association between cardiometabolic risk factors (hypertension, diabetes mellitus, hypercholesterolemia/dyslipidemia, HDL cholesterol, LDL cholesterol, lipoprotein(a), and triglycerides) and non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: Pertinent publications were identified through a systematic search in PubMed and EMBASE databases, without language restrictions. The pooled odds ratios (OR) and standardized mean differences (SMD), with their 95% confidence intervals (95% CI) were estimated using random effects (DerSimonian Laird) models, as appropriate. A set of subgroup analyses and meta-regression analysis models were performed. RESULTS: Twenty-one studies (including 1560 patients with NAION and 2292 controls), examining the association between NAION and cardiometabolic risk factors, were eligible for the systematic review and meta-analysis. Hypertension (pooled OR = 1.50; 95% CI: 1.16-1.94), diabetes mellitus (pooled OR = 1.71; 95% CI: 1.33-2.21), and hypercholesterolemia/dyslipidemia (pooled OR = 2.00; 95% CI: 1.53-2.62) were associated with NAION. Among the components of dyslipidemia, higher serum triglycerides were associated with NAION, with a medium effect size (SMD = + 0.58, 95% CI: + 0.12 to + 1.04), whereas synthesis of four studies reporting on HDL and LDL cholesterol did not reveal any significant associations. A significant association between NAION and higher serum lipoprotein(a) levels (pooled OR = 2.88; 95%CI: 1.01-8.21) was also noted. CONCLUSIONS: This systematic review and meta-analysis found that NAION was associated with cardiometabolic factors, suggesting that vascular dysfunction may be implicated in the pathogenesis of the disease. Our findings may alert health care providers to try modifying these risk factors for NAION prevention.

Sexual abuse and post-traumatic stress disorder in childhood, adolescence and young adulthood: a systematic review and meta-analysis.

Child sexual abuse (CSA) has been associated with mental health disorders throughout life during childhood, adolescence and adulthood; one of the most prevalent mental health conditions after CSA is post-traumatic stress disorder (PTSD). The present systematic review and meta-analysis aims to examine the association between CSA and PTSD in children and adolescents, evaluating also the role of potential effect modifiers, such as gender and geographic region. Participants were sexually abused (vs. CSA-free) children, adolescents and young adults, up to 21 years of age, with or without a PTSD diagnosis. Settings of eligible studies spanned school, college, university, community, hospital and non-hospital mental health facilities. Eligible studies were sought in PUBMED, ΕΜΒΑSE, PSYCINFO and GOOGLE SCHOLAR databases; end-of-search was set at August 31, 2020. Random-effects (DerSimonian-Laird) models were used for the pooling of studies. Results were reported as pooled odds ratios (OR) and 95% confidence intervals (95% CIs). Twenty-eight studies were identified, including a total cohort of 28,693 subjects. CSA was strongly associated with PTSD, at a similar extent in boys (pooled OR = 2.86, 95% CI 2.09-3.91) and girls (pooled OR = 2.38, 95% CI 1.76-3.23); meta-regression with gender confirmed the non-significant effect of gender. The association was present in all examined geographic regions. CSA is strongly associated with PTSD in childhood, adolescence and young adulthood, irrespectively of gender. Future studies should opt for thorough assessment of confounders and examine regions with paucity of studies, such as East Asia and Latin America.

Sonothrombolysis in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials. METHODS: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time. RESULTS: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03-4.54]; adjusted OR, 2.33 [95% CI, 1.02-5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68-6.11]; adjusted OR, 2.55 [95% CI, 0.76-8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented. CONCLUSIONS: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.

Psychosocial health of adolescents in relation to underweight, overweight/obese status: the EU NET ADB survey.

BACKGROUND: Both deviations from normal weight, namely, underweight and overweight/obese status, have been inversely associated with psychosocial health in adolescents. This study aimed to examine the relationship between psychosocial health and body mass index (BMI) among adolescents in five European countries, while assessing the effect of sociodemographic variables. METHODS: A cross-sectional school-based study of adolescents aged 14-17.9 years was conducted in the framework of the European Network for Adolescent Addictive Behavior survey. Self-reported questionnaires from Greece, Iceland, the Netherlands, Romania and Spain were used for the current analysis. Associations between Youth Self-Report (YSR) scales and BMI status were investigated by multiple logistic regression analysis. The effect of sociodemographic variables was also measured. RESULTS: Τhe sample consisted of 7005 adolescents aged 14-17.9 years. Borderline/clinical scores on some YSR scales were independently associated with overweight/obesity, specifically total problems (OR = 1.52, 95% CI: 1.18-1.96), internalizing ( OR = 1.48, 95% CI: 1.16-1.91), externalizing (OR = 1.36, 95% CI: 1.10-1.68), social (OR = 1.67, 95% CI: 1.19-2.35) and thought problems (OR = 1.62, 95% CI: 1.20-2.20). Among subscales, overweight/obesity specifically correlated with anxiety/depression (OR = 1.83, 95% CI: 1.33-2.51), withdrawal/depression (OR = 1.58, 95% CI: 1.02-2.48) and rule-breaking behavior (OR = 1.55, 95% CI: 1.15-2.08). Underweight was associated with problems on activities (OR = 1.31, 95% CI: 1.01-1.68) and withdrawal/depression (OR = 1.95, 95% CI: 1.27-3.01). CONCLUSIONS: Lower levels of psychosocial health are associated with both deviations from normal weight. These findings suggest the need for health policies that target health habits and lifestyle, as well as positive attitudes towards the body image, with respect to the different psychosocial characteristics of each body weight status category.

The impact of socioeconomic and environmental determinants on Mediterranean diet adherence: a municipal-level spatial analysis in Athens metropolitan area, Greece.

The aim of this study was to identify the geographical variability, the socio-economic and the environmental determinants of adherence to the Mediterranean diet in a general population sample. Level of adherence to the Mediterranean diet was estimated by the ATTICA epidemiological study for 2,749 participants, while socio-economic, demographic, and environmental characteristics were provided by official national and international databases. Higher adherence to the Mediterranean diet was detected in areas with a greater proportion of females and older people, with lower unemployment rate and immigrant population, as well as, in areas covered at a greater extent by green and with higher frequency of supermarkets and street markets. The present findings provide evidence for policy makers to better understand how layers of influence intersect to shape individuals' eating habits, while they may also contribute in identifying areas of emerging interventions needed.

Hematological findings and complications of COVID-19.

COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

Prevalence of asthma symptoms and association with obesity, sedentary lifestyle and sociodemographic factors: data from the Hellenic National Action Plan for the assessment, prevention and treatment of childhood obesity (MIS301205).

Objectives: To evaluate the prevalence of asthma symptoms in a representative sample of Greek schoolchildren and to evaluate its association with overweight/obesity as well as other socioeconomic, demographic, and lifestyle factors. Methods: This is a cross-sectional study conducted from 10/2012 to 12/2013 on a pre-selected, representative elementary school cohort. Parents completed standardized questionnaires evaluating among others socioeconomic and sedentary activity habits. Students were measured with high sensitivity methods. Socioeconomic status (SES) index (range: 0-13) was calculated on years of parental education, rented versus owned residence, size of residence evaluated as meters squared per person (m2/person), and number of vehicles. Asthma was defined according to the approved Greek version of the International Study on Allergies and Asthma in Childhood (ISAAC) criteria. Results: The prevalence of any asthma symptoms was documented in 31% of population. The odds of presenting any asthma symptoms decreased with increase in age (odds ratio: 0.96, 95% CI: 0.94-0.98) and increased with overweight (odds ratio: 1.13, 95% CI: 1.03-1.25), obesity (odds ratio: 1.27, 95% CI: 1.11-1.46) and sedentary lifestyle. Conclusion: This is the first representative survey of prevalence of asthma symptoms in children and adolescents in Greece indicating its continuous increase. A strong association between presence of asthma symptoms and obesity and sedentary activities was documented irrespectively of socioeconomic and regional factors. The findings stress the importance of public health policies toward obesity prevention and enhancement of physical activities in pediatric populations.

Effects of Body Mass Index (BMI), demographic and socioeconomic factors on organized physical activity (OPA) participation in children aged 6-15 years: a cross-sectional study comparing primary and secondary school children in Greece.

BACKGROUND: The aim of the present study was to examine the influence of body mass index category, as well as of demographic and socioeconomic factors on the participation in organized physical activity (OPA) of schoolchildren attending primary and secondary school in Greece. Furthermore, to compare the difference between the two levels. METHODS: This is a cross-sectional study conducted on a representative elementary and secondary school cohort, derived using stratification and probability proportional to size (PPS) methodology. The final sample included 18,264 subjects, aged 6 to 15 years. Parents of all students and students of secondary schools fulfilled validated questionnaires evaluating socioeconomic status, and participation to OPA. International Obesity Task Force (IOTF) cut offs were used to classify the children. Univariate and multivariate logistic models examined factors associated with OPA. All analyses were stratified by school level. RESULTS: Sport participation was not reported in 37.7 and 54.4% of primary and secondary schoolchildren respectively. Having BMI within normal range, being male, having parents participating in an organized activity and a high socio-economic status seem to encourage participation in OPA in both school levels. CONCLUSIONS: Children with normal BMI are more likely to participate in OPA. Parents as role model as well as higher socioeconomic status of the family emerge as important influencers. Participation in OPA declines as students enter secondary school. Interventions focusing on increasing physical education and activity into school daily program should be tailored to the specific needs of different weight categories and can possibly eliminate the impact of SES inequalities.

Response of an oncology unit in the midst of the COVID-19 outbreak.

Coronavirus disease 19 (COVID-19) pandemic has caused an emergency in health systems worldwide. Apart from its apparent morbidity and mortality, COVID-19 has also imposed unique challenges in the management of cancer patients. We report here measures taken by a major oncology Unit in Greece to continue operation of the department while ensuring safety of the patients and health care professionals. The efficacy of these measures could serve as guidance for Oncology departments in view of a second wave of COVID-19 cases.

Anthropometric characteristics, physical activity and risk of hematological malignancies: A systematic review and meta-analysis of cohort studies.

Overweight/obesity, adult attained height and physical activity are possible risk factors for hematological malignancies. This meta-analysis aims to evaluate the associations between these factors and hematological cancer risk in adults. Eligible cohort studies were sought in PubMed up to May 31, 2016; overall, 44 studies were included in the present analyses. Pooled relative risk estimates were calculated using random-effects models; separate analyses were conducted for non-Hodgkin lymphoma (NHL) and subtypes (diffuse large B-cell lymphoma, DLBCL; follicular cell lymphoma; small lymphocytic lymphoma/chronic lymphocytic leukemia, SLL/CLL), Hodgkin lymphoma (HL), multiple myeloma (MM), leukemia and subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, AML). Obesity was associated with increased risk of NHL, HL, MM, leukemia overall and AML in both sexes, as well as with higher DLBCL risk in women; the dose-response meta-regression analysis confirmed these associations. Less pronounced effects were observed regarding overweight, as it was associated with increased MM risk in both sexes, NHL risk in males, DLBCL and overall leukemia risk in females. Taller men presented with significantly higher risk of NHL and taller women were affected by higher risk of NHL, DLBCL, FL, CLL/SLL, MM, leukemia and AML. On the other hand, physical activity and abdominal fatness were not associated with the risk of hematological malignancies. In conclusion, this meta-analysis highlights the pivotal role of anthropometric measures in shaping the risk of hematological malignancies in adults. Additional, well-designed studies stemming from all the continents are needed for the further substantiation and generalization of the results.

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC).

OBJECTIVES: Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium. METHODS: We pooled 11 case-control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses. RESULTS: ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses. CONCLUSIONS: In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.

Alcohol consumption and risk of hematological malignancies: A meta-analysis of prospective studies.

Current convincing evidence suggests that alcohol intake increases the risk of several carcinomas, which might subsequently lead to a recommendation toward limiting alcohol consumption. However, there are accumulating data worth meta-analyzing that show a different effect on the risk of hematological malignancies. Eligible cohort studies were sought in PubMed database up to August 31, 2016. Separate analyses were performed by subtype of hematological malignancy (non-Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and subtypes), time status (ever, current, former), level of consumption (light, moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine) and gender. Moderate and heavy alcohol consumption were significantly associated with reduced risk of NHL (relative risk [RR] = 0.85, 95% confidence interval [CI]: 0.80-0.90 and RR = 0.73, 95%CI: 0.60-0.89, respectively); a protective trend was also shown for light alcohol intake (RR = 0.93, 95%CI: 0.87-1.00). Specifically, beer consumption was associated with reduced NHL risk (RR = 0.88, 95%CI: 0.81-0.95). However, the association regarding other alcoholic beverages seemed null. The beneficial effects of alcohol mainly pertained to Diffuse Large B-Cell Lymphoma (DLBCL) (RR = 0.83, 95%CI: 0.77-0.89) and Follicular Lymphoma (FL) (RR = 0.85, 95%CI: 0.78-0.93). There was also no association between alcohol consumption and risk of HL or leukemias. In contrast to most solid malignancies, alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and FL subtypes, with beer being notably beneficial.

Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0 Hepatic Resection of Colorectal Metastases: A Systematic Review and Meta-analysis.

OBJECTIVE: To examine the impact of surgical margin width on survival following R0 hepatic resection for colorectal metastases (CRLM). SUMMARY OF BACKGROUND DATA: Although negative resection margin is considered of paramount importance for the prognosis of patients with colorectal liver metastases, optimal resection margin width remains controversial. METHODS: Eligible studies examining the association between margin status after R0 hepatic resection for CRLM and survival, including overall survival (OS) and disease-free survival (DFS) were sought using the Medline, Cochrane, and EMBASE databases. Random-effects models were used for the calculation of pooled relative risks (RRs) with their 95% confidence intervals (95% CIs). RESULTS: Thirty-four studies were deemed eligible for inclusion representing a cohort of 11,147 hepatic resections. Wider resection margin (>1 vs <1 cm) was significantly associated with improved OS at 3 years (pooled RR = 0.86, 95% CI: 0.79-0.95), 5 years (pooled RR = 0.91, 95% CI: 0.85-0.97), and 10 years (pooled RR = 0.94, 95% CI: 0.88-1.00). Similarly, DFS was positively associated with >1 cm resection margin at 3, 5, and 10 years. Interestingly, >1 mm (vs <1 mm) resection margin was significantly associated with improved OS at all-time points. Meta-regression analyses did not reveal any significant modifying role of the study features under investigation, such as the administration of neoadjuvant/adjuvant therapy. CONCLUSIONS: Importantly, our findings suggest that while a >1 mm margin is associated with better prognosis than a submillimeter margin, achieving a margin >1 cm may result in even better oncologic outcomes and should be considered if possible.

Micronutrient Intake and Risk of Hematological Malignancies in Adults: A Systematic Review and Meta-analysis of Cohort Studies.

There has been accumulating evidence that several micronutrients may play a protective role in the risk of solid cancers. However, their role in hematological malignancies remains to be elucidated; this meta-analysis aims to evaluate the associations between micronutrient intake as well as supplementation and risk of hematological cancer in adults. Eligible cohort studies (examining intake of vitamin A, vitamin C, vitamin D, vitamin E, lycopene, folate, iron, carotenoids, beta-carotene, selenium, pyridoxine) were sought in PubMed up to July 31, 2016. Random-effects models were used for the calculation of pooled relative risks (RR) with their 95% confidence intervals (CI). Twelve cohort studies were deemed eligible. Null associations were noted regarding supplemented vitamin A (pooled relative risk [RR] = 0.92, 95% confidence interval [CI]: 0.80-1.07), supplemented vitamin C (pooled RR = 1.00, 95%CI: 0.90-1.12), total vitamin D (pooled RR = 1.05, 95%CI: 0.91-1.20), supplemented vitamin E (pooled RR = 0.98, 95%CI: 0.88-1.10), and dietary lycopene intake (pooled RR = 1.00, 95%CI: 0.86-1.16) and the risk of non-Hodgkin lymphoma. No summary estimates are provided for other hematological malignancies due to the limited number of studies. Future prospective trials should be conducted for a better understanding of this field; especially regarding Hodgkin lymphoma, leukemia and plasma cell neoplasms, on which data are scarce.

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic ischemic stroke or transient ischemic attack has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta-analytical approach. METHODS: We performed a systematic literature review to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD, or both compared to the gold standard of TEE. RESULTS: Our literature search identified 35 eligible studies including 3,067 patients. The pooled sensitivity and specificity for TCD was 96.1% (95% confidence interval [CI] = 93.0-97.8%) and 92.4% (95% CI = 85.5-96.1%), whereas the respective measures for TTE were 45.1% (95% CI = 30.8-60.3%) and 99.6% (95% CI = 96.5-99.9%). TTE was superior in terms of higher positive likelihood ratio values (LR+ = 106.61, 95% CI = 15.09-753.30 for TTE vs LR+ = 12.62, 95% CI = 6.52-24.43 for TCD; p = 0.043), whereas TCD demonstrated lower negative likelihood values (LR- = 0.04, 95% CI = 0.02-0.08) compared to TTE (LR- = 0.55, 95% CI = 0.42-0.72; p < 0.001). Finally, the area under the summary receiver operating curve (AUC) was significantly greater (p < 0.001) in TCD (AUC = 0.98, 95% CI = 0.97-0.99) compared to TTE studies (AUC = 0.86, 95% CI = 0.82-0.89). INTERPRETATION: TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE.

Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility.

BACKGROUND: Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer. OBJECTIVES: To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer. SEARCH METHODS: A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions. SELECTION CRITERIA: Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible. DATA COLLECTION AND ANALYSIS: Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I2. Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer. MAIN RESULTS: Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated with an increased risk of endometrial cancer (RR 0.96, 95% CI 0.67 to 1.37; 156,774 participants; very low quality evidence). Fifteen eligible studies, using a general population as the control group, found an increased risk after exposure to any ovary-stimulating drug (RR 1.75, 95% CI 1.18 to 2.61; 1,762,829 participants; very low quality evidence).Five eligible studies, confined to subfertile women (92,849 participants), reported on exposure to clomiphene citrate; the pooled studies indicated a positive association ( RR 1.32; 95% CI 1.01 to 1.71; 88,618 participants; very low quality evidence), although only at high dosage (RR 1.69, 95% CI 1.07 to 2.68; two studies; 12,073 participants) and at a high number of cycles (RR 1.69, 95% CI 1.16 to 2.47; three studies; 13,757 participants). Four studies found an increased risk of endometrial cancer in subfertile women who required clomiphene citrate compared to a general population control group (RR 1.87, 95% CI 1.00 to 3.48; four studies, 19,614 participants; very low quality evidence). These data do not tell us whether the association is due to the underlying conditions requiring clomiphene or the treatment itself.Using unexposed subfertile women as controls, exposure to gonadotropins was associated with an increased risk of endometrial cancer (RR 1.55, 95% CI 1.03 to 2.34; four studies; 17,769 participants; very low quality evidence). The respective analysis of two studies (1595 participants) versus the general population found no difference in risk (RR 2.12, 95% CI 0.79 to 5.64: very low quality evidence).Exposure to a combination of clomiphene citrate and gonadotropins, compared to unexposed subfertile women, produced no difference in risk of endometrial cancer (RR 1.18, 95% CI 0.57 to 2.44; two studies; 6345 participants; very low quality evidence). However, when compared to the general population, an increased risk was found , suggesting that the key factor might be subfertility, rather than treatment (RR 2.99, 95% CI 1.53 to 5.86; three studies; 7789 participants; very low quality evidence). AUTHORS' CONCLUSIONS: The synthesis of the currently available evidence does not allow us to draw robust conclusions, due to the very low quality of evidence. It seems that exposure to clomiphene citrate as an ovary-stimulating drug in subfertile women is associated with increased risk of endometrial cancer, especially at doses greater than 2000 mg and high (more than 7) number of cycles. This may largely be due to underlying risk factors in women who need treatment with clomiphene citrate, such as polycystic ovary syndrome, rather than exposure to the drug itself. The evidence regarding exposure to gonadotropins was inconclusive.

Vulvar, Perianal and Perineal Cancer After Hidradenitis Suppurativa: A Systematic Review and Pooled Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that frequently involves the perineal and perianal regions. The association between HS and malignant transformation is a rare but under recognized phenomenon. OBJECTIVE: This systematic review aims to summarize all available cases of vulvar and perianal/perineal cancer emerging in patients with HS, describing clinical and therapeutic particularities of these coexisting conditions in female patients. MATERIALS AND METHODS: This systematic review and pooled analysis was performed in accordance with the PRISMA guidelines; end-of-search date was June 15, 2015. RESULTS: A total of 13 eligible articles were identified; 7 cases of vulvar cancer and 6 cases of perineal/perianal carcinomas in patients with HS were noted. A majority of published cases pertained to rather advanced carcinomas; only occasionally early stage carcinomas were identified. The optimal modifications in the treatment scheme of vulvar, perianal, and perineal cancer in patients with HS have not been established; detailed reporting of recurrence- and survival-related aspects is advised. CONCLUSION: Vulvar, perianal, and perineal cancer represent a rare but serious complication of HS.

Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece.

BACKGROUND: Data on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire. METHODS: A questionnaire on drug allergy was accessible online for a 3-month period. Participants voluntarily answered 28 questions referring to: suspected drug, clinical manifestations, concomitant factors, received treatment, reaction's re-occurrence. RESULTS: A total of 2528 questionnaires were included in study analysis. Beta-lactams and non-steroidal anti-inflammatory drugs were the most prevalent culprit agents (53% and 27.5% respectively) while half of the participants acknowledged skin manifestations as the most common symptoms. One out of three reported subsequent exposure to the drug presumed to be responsible for the reaction and 74.5% of those stated a new reaction upon re-exposure. Only 26.7% underwent allergological evaluation. Reactions manifested with respiratory or cardiovascular symptoms, parenteral administration of the culprit drug and personal history of allergy to agents of >1 different pharmacological categories were associated with increased risk of hospitalization. CONCLUSIONS: Allergic reactions to drugs are adverse events difficult to define and diagnose. A remarkable proportion of presumed as hypersensitivity reactions are not referred to allergists; therefore these patients may be either re-exposed to potentially noxious drugs, or needlessly avoid whole classes of drugs as b-lactams for more costly or less appropriate treatments. Internet-based questionnaires may contribute to awareness programs concerning drug allergy and help improve proper referral.