International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study.

BACKGROUND: Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. OBJECTIVE: In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. METHODS: Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. RESULTS: We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. CONCLUSIONS: We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

Migrant agricultural workers' deaths in Ontario from January 2020 to June 2021: a qualitative descriptive study.

BACKGROUND: Nine migrant agricultural workers died in Ontario, Canada, between January 2020 and June 2021. METHODS: To better understand the factors that contributed to the deaths of these migrant agricultural workers, we used a modified qualitative descriptive approach. A research team of clinical and academic experts reviewed coroner files of the nine deceased workers and undertook an accompanying media scan. A minimum of two reviewers read each file using a standardized data extraction tool. RESULTS: We identified four domains of risk, each of which encompassed various factors that likely exacerbated the risk of poor health outcomes: (1) recruitment and travel risks; (2) missed steps and substandard conditions of healthcare monitoring, quarantine, and isolation; (3) barriers to accessing healthcare; and (4) missing information and broader issues of concern. CONCLUSION: Migrant agricultural workers have been disproportionately harmed by the COVID-19 pandemic. Greater attention to the unique needs of this population is required to avoid further preventable deaths.

Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study.

BACKGROUND: The atopic march describes the progression from atopic dermatitis during infancy to asthma and allergic rhinitis in later childhood. In a Canadian birth cohort we investigated whether concomitant allergic sensitization enhances subsequent development of these allergic diseases at age 3 years. METHODS: Children completed skin prick testing at age 1 year. Children were considered sensitized if they produced a wheal 2 mm or larger than that elicited by the negative control to any of 10 inhalant or food allergens. Children were also assessed for atopic dermatitis by using the diagnostic criteria of the UK Working Party. At age 3 years, children were assessed for asthma, allergic rhinitis, food allergy, and atopic dermatitis. Data from 2311 children were available. RESULTS: Atopic dermatitis without allergic sensitization was not associated with an increased risk of asthma at age 3 years after adjusting for common confounders (relative risk [RR], 0.46; 95% CI, 0.11-1.93). Conversely, atopic dermatitis with allergic sensitization increased the risk of asthma more than 7-fold (RR, 7.04; 95% CI, 4.13-11.99). Atopic dermatitis and allergic sensitization had significant interactions on both the additive (relative excess risk due to interaction, 5.06; 95% CI, 1.33-11.04) and multiplicative (ratio of RRs, 5.80; 95% CI, 1.20-27.83) scales in association with asthma risk. There was also a positive additive interaction between atopic dermatitis and allergic sensitization in their effects on food allergy risk (relative excess risk due to interaction, 15.11; 95% CI, 4.19-35.36). CONCLUSIONS: Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years.

Diagnosing atopic dermatitis in infancy: Questionnaire reports vs criteria-based assessment.

BACKGROUND: Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years. METHODS: Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports. RESULTS: Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report. CONCLUSIONS: These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).

Timing of food introduction and development of food sensitization in a prospective birth cohort.

BACKGROUND: The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study. METHODS: Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18, and 24 months were used to determine timing of introduction of cow's milk products, egg, and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white, and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort. RESULTS: Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg, and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adjOR 3.69, 95% CI 1.37-9.08; egg adjOR 1.89, 95% CI 1.25-2.80; peanut adjOR 1.76, 95% CI 1.07-3.01). Latent class analysis produced a three-class model: early, usual, and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adjOR 1.78, 95% CI 1.26-2.49). CONCLUSIONS: Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases.

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Iliac vein stenting is safe when performed in an office based laboratory setting.

BACKGROUND: Venous stenting for iliac vein outflow obstruction is associated with excellent long-term stent patency and symptom resolution. However, the safety of iliac vein stenting performed in an office-based laboratory (OBL) setting is not well-defined. The purpose of our investigation was to determine the safety profile of iliac vein stenting in an OBL setting. METHODS: Data were prospectively collected in the Center for Vascular Medicine electronic medical record system (NextGen Healthcare Information System, Irvine, Calif) and retrospectively analyzed. Standardized patient safety and sedation protocols were used in accordance with the accreditation standards of the Joint Commission for Accreditation of Hospital Organizations for office-based surgery centers. Patient consultations, interventions, and follow-up at 1 to 6 weeks were included in the present analysis. All the patients had received moderate sedation during their procedure. Complications requiring hospitalization were classified as major complications. Minor complications consisted of bleeding, hematoma, vasovagal response, in-stent thrombosis resulting in complete occlusion of the iliac vein stent, an allergic reaction, hematemesis, hypotension, pelvic discomfort, and pseudoaneurysm. RESULTS: Between January 2015 and January 2019, 1223 iliac vein stents were placed in 1104 patients (23.7% male; 76.3% female). A total of 90 minor complications (7.36%) and 5 major complications (0.41%) were observed. The major complications included the following: one allergic reaction, one episode of atrial fibrillation, one episode of supraventricular tachycardia, one episode of chest pain, and one case of acute stent occlusion. The minor complications were primarily insertion site hematomas. No complications were related to sedation or acute renal failure. No patient died. CONCLUSIONS: Major complications were rare after iliac vein stenting in an OBL setting. Minor complications were primarily insertion site hematomas, which did not require inpatient hospitalization. Our analysis has shown that iliac vein stenting in an OBL setting is a safe and well-tolerated procedure.

Immediate postprocedure anticoagulation with factor Xa inhibitors of venous stents for nonthrombotic venous lesions does not increase stent patency.

BACKGROUND: Many clinicians will prescribe anticoagulation therapy for patients after iliac vein stenting to prevent early or late stent thrombosis. At present, it is unknown whether therapeutic anticoagulation has any effect on stent patency. Thus, we assessed the role of short-term anticoagulation on iliac vein stent patency in patients with nonthrombotic iliac vein lesions (NIVLs). METHODS: We performed a retrospective medical record review of all iliac vein stents placed for NIVLs at the Center for Vascular Medicine from January 2018 to December 2019. We compared the stent patency in the two groups. The anticoagulation (AC) group had received rivaroxaban or apixaban postoperatively for a minimum of 90 days and were compared with a group that had received no postoperative anticoagulation (NAC). Stent patency was assessed using transabdominal ultrasound at 3, 6, 12, 18, 24, and 30 months. At the discretion of the treating physician, the patients who demonstrated thrombus layering on surveillance ultrasound scanning continued rivaroxaban or apixaban until thrombus resolution was observed. The demographics and stent location, diameter, and length were assessed. Stent patency was analyzed using life table analyses. Differences in stent patency were analyzed using GraphPad Prism, version 8, statistical software (GraphPad Software Inc, La Jolla, Calif) and the log-rank (Mantel-Cox) test. RESULTS: The number of patients and stents in each group were as follows: AC group, 299 patients and 308 stents; and NAC group, 77 patients and 90 stents. The average age was 52.24 ± 13.44 years and 55.63 ± 14.49 years in the AC and NAC groups, respectively (P ≤ .065). Women constituted 76% of the patients in the AC group and 72% in the NAC group. The average stent diameter and length for the AC group was 20 ± 2 mm and 77 ± 13 mm and for the NAC group was 19 ± 2 mm and 82 ± 9 mm, respectively. The stents had been placed in the right common iliac vein, bilaterally, or left common iliac vein territory in 15%, 3%, and 82% in the AC group and 18%, 2%, and 80% in the NAC group, respectively. The cumulative stent patency at 30 months was 98.7% and 94.6% for the NAC and AC groups, respectively (P ≤ .83). All the stents placed were Wallstents (Boston Scientific, Marlborough, Mass). A total of eight insertion site thromboses occurred that did not affect stent patency: five in the AC group (1.6%) and three in the NAC group (4.5%; P = .15). In addition, 19 patients demonstrated evidence of thrombus layering, with 6 receiving extended anticoagulation. CONCLUSIONS: Our data indicate that perioperative stent thrombosis in patients with NIVLs is uncommon. Thus, anticoagulation for perioperative stent thrombosis prophylaxis is not necessary. Anticoagulation should only be used for patients with insertion site thromboses and should be considered if thrombus layering is observed on surveillance scanning.

Development of a Symptom-Based Tool for Screening of Children at High Risk of Preschool Asthma.

Importance: Despite advances in asthma therapeutics, the burden remains highest in preschool children; therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings. Objective: To develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden. Design, Setting, and Participants: The cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022. Exposures: The CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age. Main Outcomes and Measures: Within the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values. Results: Among 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years; 1324 [52.7%] male; 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94; 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73; 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70; 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82; 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87; 95% CI, 0.80-0.94). Conclusions and Relevance: In this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.

Presentation patterns in women with pelvic venous disorders differ based on age of presentation.

BACKGROUND: The prevalence and presentation patterns in women with pelvic venous disorders (PeVD) secondary to pelvic venous insufficiency (PVI) at various ages are ill-defined. The purpose of this investigation was to determine if the types of symptoms, interventions, and treatment outcomes of women with PeVD varied with age progression. METHODS: From January 2015 to December 2019, we retrospectively reviewed prospectively collected data on 1,280 women with PeVD from our electronic medical record at the Center for Vascular Medicine (CVM). Medical and surgical comorbidities, past medical history, presenting pelvic and lower extremity symptoms, Clinical, Etiology, Anatomy, Pathophysiology (CEAP) class, revised Venous Clinical Severity Score (rVCSS), visual analog pain score (VAS) and types of interventions were assessed. Patients were grouped into five categories based on age of initial presentation: 20-29, 30-39, 40-49, 50-59, and greater than or equal to 60. Patients were also subcategorized according to their course of treatment: Iliac venous stenting alone, ovarian vein embolization (OVE) alone, simultaneous iliac vein stenting and ovarian vein embolization, and staged iliac vein stenting and ovarian vein embolization. Differences in groups were analyzed utilizing chi square, analysis of variance and regression analysis with Graphpad Prism 8 (San Diego, CA) and SAS Studio 3.8 (Cary, NC) statistical software. RESULTS: From January 2015 through December 2019, 1,280 women were treated for PeVD. The average ages in each group were the following: 26.53 ± 2.90 (n = 57), 35.80 ± 2.84 (n = 238), 44.98 ± 2.78 (n = 345), 54.67 ± 2.90 (n = 324) and 68.39 ± 8.44 (n = 316) respectively. The prevalence of PVI by age group was 4.45%,18.59%, 26.95%, 25.31% and 24.70% respectively (p < 0.05). The prevalence of diabetes, hypertension, coronary artery disease (CAD) and hypercholesterolemia differed between age groups (p < 0.05). Significant differences in the prevalence of pelvic pain, dyspareunia, dysmenorrhea, vulvar varices, leg pain, leg edema, leg heaviness, restless legs, varicose veins, and leg ulcers were observed across treatment groups (p < 0.05). CEAP distribution differed by age with CEAP 0-2 decreasing with age, CEAP 3 progressively increasing with age and CEAP 4-6 predominantly observed in patients older than 50. Analysis of variance indicated that with each decile increase in age, the prevalence of leg symptoms increased (p < 0.05) with a reciprocal decrease in pelvic symptoms (p < 0.05). All intervention types were infrequent in twenty year old's. There was a linear increase in stenting with each decile increase in age. The prevalence of OVE was similar across all age groups. There was an overall improvement in VAS scores for all treatment and age groups. For patients in their 20 s, an initial improvement in VAS scores was observed with moderate recurrence of pain observed after three months. CONCLUSION: PeVD presents as a spectrum of signs and symptoms, with pelvic and leg symptoms being inversely related according to age. The prevalence of PeVD is lowest in patients in their twenties with differences in presentation observed with increasing age. Venous stenting progressively increases with each decile of age whereas the prevalence of OVE is similar regardless of age. There is overall improvement in symptoms post intervention, although women in their 20 s do not respond as well to intervention as women in other age groups. Future investigations will focus on determining which pelvic venous lesion is the predominant factor that needs correction to achieve maximal pain reduction.

Innovations in suicide assessment and prevention during pandemics.

Emerging evidence, based on the synthesis of reports from past infectious disease-related public health emergencies, supports an association between previous pandemics and a heightened risk of suicide or suicide-related behaviours and outcomes. Anxiety associated with pandemic media reporting appears to be one critical contributing factor. Social isolation, loneliness, and the disconnect that can result from public health strategies during global pandemics also appear to increase suicide risk in vulnerable individuals. Innovative suicide risk assessment and prevention strategies are needed to recognise and adapt to the negative impacts of pandemics on population mental health.

Reduced peanut sensitization with maternal peanut consumption and early peanut introduction while breastfeeding.

New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother-child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14-0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01-0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this "triple exposure" hypothesis.

The Impact of Infectious Disease-Related Public Health Emergencies on Suicide, Suicidal Behavior, and Suicidal Thoughts.

Background: Infectious disease-related public health emergencies (epidemics) may increase suicide risk, and high-quality evidence is needed to guide an international response. Aims: We investigated the potential impacts of epidemics on suicide-related outcomes. Method: We searched MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Web of Science, PsyArXiv, medRxiv, and bioRxiv from inception to May 13-16, 2020. Inclusion criteria: primary studies, reviews, and meta-analyses; reporting the impact of epidemics; with a primary outcome of suicide, suicidal behavior, suicidal ideation, and/or self-harm. Exclusion criteria: not concerned with suicide-related outcomes; not suitable for data extraction. PROSPERO registration: #CRD42020187013. Results: Eight primary papers were included, examining the effects of five epidemics on suicide-related outcomes. There was evidence of increased suicide rates among older adults during SARS and in the year following the epidemic (possibly motivated by social disconnectedness, fears of virus infection, and concern about burdening others) and associations between SARS/Ebola exposure and increased suicide attempts. A preprint study reported associations between COVID-19 distress and past-month suicidal ideation. Limitations: Few studies have investigated the topic; these are of relatively low methodological quality. Conclusion: Findings support an association between previous epidemics and increased risk of suicide-related outcomes. Research is needed to investigate the impact of COVID-19 on suicide outcomes.

Spine stabilization is a risk factor for the development of pelvic iliac vein lesions.

BACKGROUND: Open lumbar spine stabilization surgery often requires mobilization of the left and right common iliac veins (CIVs) and the placement of plates and screws that can impinge on them. We reviewed our venography experience of the past 3 years to determine whether there is an association between spine stabilization surgery and the development of symptomatic iliac vein outflow lesions. METHODS: A retrospective chart review of prospectively collected data from our electronic medical record system was performed to identify patients who underwent venography with or without venous stenting and had a history of previous lumbar spine stabilization. Patients' demographics, medical comorbidities, venograms, and intravascular ultrasound (IVUS) data were collected and analyzed. The senior author reviewed all venograms and IVUS images of patients with previous spine stabilization procedures. RESULTS: From January 2014 to April 2018, venography was performed in 1713 limbs in 1245 patients at the Center for Vascular Medicine. Of the 1245 patients, 18 patients had a history of lumbar spine stabilization procedures: five anterior-posterior and 13 posterior. Nine had single-level and eight had two- or three-level fusions. All 18 patients demonstrated pelvic lesions. These included 1 left CIV aneurysm, 5 left CIV stenoses, 3 bilateral CIV stenoses, 2 left CIV and inferior vena cava occlusions, and 2 external iliac vein stenoses. The aneurysm patient was treated with anticoagulation, 8 patients underwent stenting, 1 patient refused stenting because of relocation to another country, 1 inferior vena cava-CIV occlusion could not be crossed, fear of dislodging a thrombus and the proximity to a protruding posteriorly placed screw prevented stenting in 2 patients, and 4 patients had a venoplasty alone because of undersizing of a stenosis or missed lesions with IVUS after review by a blinded reviewer. Lesions in anterior lumbar interbody fusion patients were extremely stenotic, required predilation, and resulted in a residual stenosis requiring venoplasty at a second setting in one patient. CONCLUSIONS: Lumbar spine stabilization surgery may be a risk factor for development of symptomatic venous outflow obstruction lesions. During venography and stenting in patients with anterior lumbar interbody fusion approaches, significant scarring may be encountered, resulting in a residual stenosis after stent placement. Predilation venoplasty, before stent deployment, is recommended to prevent stent migration. Furthermore, a history of spine stabilization surgery in patients presenting with pelvic symptoms, lower extremity pain or swelling, or post-thrombotic symptoms should prompt consideration of a pelvic venous duplex ultrasound examination to determine whether an iliac venous outflow lesion is present.

Type of anti-thrombotic therapy for venous stenting in patients with non-thrombotic iliac vein lesions does not influence the development of in-stent restenosis.

BACKGROUND: In patients receiving stents for symptomatic non-thrombotic iliac vein lesions, many clinicians prescribe anti-thrombotic medications. Whether or not anti-coagulation post-venous stenting improves stent patency is unknown. The aim of this investigation is to determine whether prophylactic post-operative anti-thrombotic therapy improves stent patency and/or prevents in-stent restenosis. METHODS: The medical records and venous ultrasounds for 389 patients stented for non-thrombotic iliac vein lesions were retrospectively reviewed. Patients were categorized into three anti-thrombotic regimens: Clopidogrel, Aspirin and Clopidogrel, and Apixaban or Rivaroxaban. Patients were routinely assessed for restenosis and stent patency at 6, 26, and 52 weeks and treated with anti-thrombotics for 90 days. RESULTS: Freedom from in-stent restenosis at 6, 26, and 52 weeks were Clopidogrel (91.50, 82.91, 80.95%), Aspirin and Clopidogrel (88.68, 80.03, 80.03%), and Apixaban or Rivaroxaban (91.03, 85.11, 83.18%). Primary patencies were Clopidogrel (98.77, 98.77, 98.10%), Aspirin and Clopidogrel (100, 95.74, 95.74%), and Apixaban or Rivaroxaban (98.70, 98.70, 96.71%). There were no statistically significant differences. CONCLUSIONS: The type of post-operative anti-thrombotic therapy for non-thrombotic iliac vein lesions does not appear to improve stent patency or prevent the development of in-stent restenosis.

Cigarette consumption estimates for 71 countries from 1970 to 2015: systematic collection of comparable data to facilitate quasi-experimental evaluations of national and global tobacco control interventions.

OBJECTIVES: To collect, appraise, select, and report the best available national estimates of cigarette consumption since 1970. DESIGN: Systematic collection of comparable data. SETTING AND POPULATION: 71 of 214 countries for which searches for national cigarette consumption data were conducted, representing over 95% of global cigarette consumption and 85% of the world's population. MAIN OUTCOME MEASURES: Validated cigarette consumption data covering 1970-2015 were identified for 71 countries. Data quality appraisal was conducted by two research team members in duplicate, with greatest weight given to official government sources. All data were standardised into units of cigarettes consumed per year in each country, a detailed accounting of data quality and sourcing was prepared, and all collected data and metadata were made freely available in an open access dataset. RESULTS: Cigarette consumption fell in most countries over the past three decades but trends in country specific consumption were highly variable. For example, China consumed 2.5 million metric tonnes (MMT) of cigarettes in 2013, more than Russia (0.36 MMT), the United States (0.28 MMT), Indonesia (0.28 MMT), Japan (0.20 MMT), and the next 35 highest consuming countries combined. The US and Japan achieved reductions of more than 0.1 MMT from a decade earlier, whereas Russian consumption plateaued, and Chinese and Indonesian consumption increased by 0.75 MMT and 0.1 MMT, respectively. These data generally concord with modelled country level data from the Institute for Health Metrics and Evaluation and have the additional advantage of not smoothing year-over-year discontinuities that are necessary for robust quasi-experimental impact evaluations. CONCLUSIONS: Before this study, publicly available data on cigarette consumption have been limited; they have been inappropriate for quasi-experimental impact evaluations (modelled data), held privately by companies (proprietary data), or widely dispersed across many national statistical agencies and research organisations (disaggregated data). This new dataset confirms that cigarette consumption has decreased in most countries over the past three decades, but that secular country specific consumption trends are highly variable. The findings underscore the need for more robust processes in data reporting, ideally built into international legal instruments or other mandated processes. To monitor the impact of the WHO Framework Convention on Tobacco Control and other tobacco control interventions, data on national tobacco production, trade, and sales should be routinely collected and openly reported.

Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer.

Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions. The transcriptional status and epigenetic features of the target genes influence this effect. Importantly, inflammation-induced de novo genomic rearrangements are blocked by homologous recombination (HR) and promoted by non-homologous end-joining (NHEJ) pathways. In conjunction with the association of proliferative inflammatory atrophy (PIA) with human prostate cancer, our results support a working model in which recurrent genomic rearrangements induced by inflammatory stimuli lead to the development of prostate cancer.