Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Predictors of Post-Thrombotic Ulcer after Acute DVT: The RIETE Registry.

In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilitating and end-stage clinical expression of the post-thrombotic syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have not been identified.We used the international observational RIETE registry to assess the evolution of PTS signs and symptoms during a 3-year follow-up period and to identify independent predictors of PTS ulcer at 1 year in patients with acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2 and 3 years were 2.7% (n = 50), 4.3% (n = 54) and 7.1% (n = 60), respectively. The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable (≈40%), while the proportion of patients with PTS signs increased slightly over time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio [OR] = 5.5 [2.8-10.9]), diabetes (OR = 2.3 [1.1-4.7]), pre-existing leg varicosities (OR = 3.2 [1.7-6.1]) and male sex (OR = 2.5 [1.3-5.1]) independently increased the risk of PTS ulcer at 1 year. Obesity also increased the risk but failed to reach statistical significance (OR = 1.8 [0.9-3.3]). DVT treatment characteristics (duration or drug) did not influence the risk.Our results evidence that after acute DVT, pre-existing leg varicosities, prior venous thromboembolism, diabetes and male gender independently increased the risk for PTS ulcer. This suggests that clinicians should consider strategies aimed to prevent ulcers in high-risk DVT patients, such as preventing VTE recurrence, use of stockings in those with pre-existing venous insufficiency, careful monitoring of diabetic patients and encouraging weight loss in obese patients.

Analysis of clinical factors affecting the rates of fatal pulmonary embolism and bleeding in cancer patients with venous thromboembolism.

BACKGROUND: In cancer patients with symptomatic venous thromboembolism (VTE) (deep-vein thrombosis (DVT) and/or pulmonary embolism (PE)), clinical factors that influence the benefit-risk balance of anticoagulation need to be identified so treatment intensity and duration can be optimally adjusted for the individual patient. METHODS: Using clinical data for cancer patients with VTE obtained from the RIETE registry, we compared how rates of fatal PE and fatal bleeding during and after anticoagulation vary depending on patients' clinical characteristics. RESULTS: Data were analysed from the 10,962 cancer patients with VTE (5,740 with PE with or without DVT; 5,222 with DVT alone) in RIETE registry as of March 2016. Fatal PE occurred in 2.18% of patients, while fatal bleedings occurred in 1.55%. During the 12 months from initial VTE, fatal PE was the most common cause of death, after disseminating cancer, and bleeding the fourth most common. In patients initially presenting with PE, fatal PE during anticoagulation was 4-fold more frequent than fatal bleeding (204 vs 51 deaths) and occurred mostly during the first month of treatment (196/223, 88%). In patients initially presenting with DVT, fatal PE was 3-fold lower than fatal bleeding during (25 vs 85 deaths) and after anticoagulation treatment (8 vs 37 deaths). During the 12-month follow-up, other characteristics of cancer patients with VTE were identified as more common in fatal cases of PE and/or bleeding than in surviving cases. INTERPRETATION: Baseline clinical characteristics may determine anticoagulation outcomes in cancer patients with VTE and should be further investigated as possible factors for guiding changes in current practices of anticoagulation, such as adjusting anticoagulation intensity and duration in selected patients.

Prior thromboprophylaxis and outcome in patients experiencing acute venous thromboembolism after an acute medical illness.

BACKGROUND: Even despite the use of thromboprophylaxis, some patients with an acute medical illness develop symptomatic venous thromboembolism (VTE). It is unclear whether the outcome in these patients is different in those in whom prophylaxis was not prescribed. PATIENTS AND METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the 3-month outcome (death, fatal pulmonary embolism, VTE recurrences, major bleeding) of patients with acute VTE after immobilization for an acute medical disease, according to the use of prophylaxis. RESULTS: Thromboprophylaxis was prescribed in 1313 (37%) of the 3527 patients included in August 2014. Acute infection was the most frequent cause of immobilization. Patients who received prophylaxis were more frequently immobilized in hospital than at home (70% vs. 22%), and fewer patients were immobilized for cancer (13% vs. 22%). During the first 3months of treatment, the rates of all-cause death (23 vs. 21%), fatal PE (2.6 vs. 3.1%), VTE recurrences (2.4% vs. 2.8%), and major bleeding (4.2% for both) did not differ between the two groups. Thromboprophylaxis was not associated with each outcome in multivariate analysis. CONCLUSIONS: The outcome in patients with VTE provoked by medical immobilization was not influenced by the use of thromboprophylaxis during the period of immobility.

Gender differences in cancer patients with acute venous thromboembolism.

BACKGROUND: The outcome of cancer patients with acute venous thromboembolism (VTE) may differ according to gender. METHODS: We used the RIETE database to compare the rate of VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) recurrences), major bleeding and mortality during the course of anticoagulation, according to gender. RESULTS: As of August 2014, 11,055 patients with active cancer were enrolled in RIETE, of whom 5,104 (46%) were women. During the course of anticoagulation (mean: 142 days), 505 patients developed recurrent VTE, 429 bled and 2730 died. Compared with men, women had a significantly lower rate of fatal bleeding (risk ratio [RR]: 0.69; 95% CI: 0.47-0.99) and death (RR: 0.90; 95% CI: 0.83-0.97), and a non-significantly lower rate of PE recurrences (RR 0.83; 95% CI: 0.65-1.06) and major bleeding (RR: 0.89; 95% CI: 0.74-1.08). CONCLUSIONS: During the course of anticoagulation, cancer women with VTE had a better outcome than men.

A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the lower limbs.

BACKGROUND: No prior studies have identified which patients with deep vein thrombosis in the lower limbs are at a low risk for adverse events within the first week of therapy. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) to identify patients at low risk for the composite outcome of pulmonary embolism, major bleeding, or death within the first week. We built a prognostic score and compared it with the decision to treat patients at home. RESULTS: As of December 2013, 15,280 outpatients with deep vein thrombosis had been enrolled. Overall, 5164 patients (34%) were treated at home. Of these, 12 (0.23%) had pulmonary embolism, 8 (0.15%) bled, and 4 (0.08%) died. On multivariable analysis, chronic heart failure, recent immobility, recent bleeding, cancer, renal insufficiency, and abnormal platelet count independently predicted the risk for the composite outcome. Among 11,430 patients (75%) considered to be at low risk, 15 (0.13%) suffered pulmonary embolism, 22 (0.19%) bled, and 8 (0.07%) died. The C-statistic was 0.61 (95% confidence interval [CI], 0.57-0.65) for the decision to treat patients at home and 0.76 (95% CI, 0.72-0.79) for the score (P = .003). Net reclassification improvement was 41% (P < .001). Integrated discrimination improvement was 0.034 for the score and 0.015 for the clinical decision (P < .001). CONCLUSIONS: Using 6 easily available variables, we identified outpatients with deep vein thrombosis at low risk for adverse events within the first week. These data may help to safely treat more patients at home. This score, however, should be validated.

Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism.

BACKGROUND: The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. RESULTS: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS: One in every three cancer patients dying of PE had recent immobilization for ≥ 4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.

BACKGROUND: In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS: The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS: MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS: The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.

Platelet count and outcome in patients with acute venous thromboembolism.

The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.

Low-molecular-weight or unfractionated heparin in venous thromboembolism: the influence of renal function.

BACKGROUND: In patients with acute venous thromboembolism and renal insufficiency, initial therapy with unfractionated heparin may have some advantages over low-molecular-weight heparin. METHODS: We used the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Registry data to evaluate the 15-day outcome in 38,531 recruited patients. We used propensity score matching to compare patients treated with unfractionated heparin with those treated with low-molecular-weight heparin in 3 groups stratified by creatinine clearance levels at baseline: >60 mL/min, 30 to 60 mL/min, or <30 mL/min. RESULTS: Patients initially receiving unfractionated heparin therapy (n = 2167) more likely had underlying diseases than those receiving low-molecular-weight heparin (n = 34,665). Propensity score-matched groups of patients with creatinine clearance levels >60 mL/min (n = 1598 matched pairs), 30 to 60 mL/min (n = 277 matched pairs), and <30 mL/min (n = 210 matched pairs) showed an increased 15-day mortality for unfractionated heparin compared with low-molecular-weight heparin (4.5% vs 2.4% [P = .001], 5.4% vs 5.8% [P = not significant], and 15% vs 8.1% [P = .02], respectively), an increased rate of fatal pulmonary embolism (2.8% vs 1.2% [P = .001], 3.2% vs 2.5% [P = not significant], and 5.7% vs 2.4% [P = .02], respectively), and a similar rate of fatal bleeding (0.3% vs 0.3%, 0.7% vs 0.7%, and 0.5% vs 0.0%, respectively). Multivariate analysis confirmed that patients treated with unfractionated heparin were at increased risk for all-cause death (odds ratio, 1.8; 95% confidence interval, 1.3-2.4) and fatal pulmonary embolism (odds ratio, 2.3; 95% confidence interval, 1.5-3.6). CONCLUSIONS: In comparison with low-molecular-weight heparin, initial therapy with unfractionated heparin was associated with a higher mortality and higher rate of fatal pulmonary embolism in patients with creatinine clearance levels >60 mL/min or <30 mL/min, but not in those with levels between 30 and 60 mL/min.

Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study.

BACKGROUNDS: AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients' characteristics, and adherence to guidelines. METHODOLOGY/PRINCIPAL FINDINGS: An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0-35%). Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%). The overall mortality rate was 11.6% (0-50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. CONCLUSIONS/SIGNIFICANCE: The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement.

Tratamiento de la linfangioleiomiomatosis con sirolimus / Lymphangioleiomyomatosis Treatment with Sirolimus

La linfangioleiomiomatosis (LAM) es una enfermedad pulmonar rara que afecta a mujeres jóvenes yque suele progresar hacia el fracaso del sistema respiratorio. No existe evidencia científica suficienteque justifique el uso de ningún fármaco en la LAM. El único tratamiento efectivo en los casos graves esel trasplante pulmonar. En la LAM se ha observado una activación de mammalian target of rapamycin(mTOR). La administración de sirolimus, un inhibidor de mTOR, parece reducir los angiomiolipomasrenales que se asocian a la LAM. Además, algunos trabajos sugieren una mejoría de la función pulmonarcon este fármaco. Presentamos tres mujeres con LAM que manifestaron un deterioro clínico y funcionalrespiratorio rápidamente progresivo y que fueron tratadas con sirolimus (AU)

Lymphangioleiomyomatosis (LAM) is a rare lung disease, that predominantly affects young females andgenerally progresses to respiratory failure. There is not sufficient evidence to support the routine useof any treatment in LAM. The only treatment for severe LAM is currently lung transplantation. Activationof mammalian target of rapamycin (mTOR) signalling pathway has been observed in LAM. LAM isoften associated with angiomyolipoma in the kidneys. mTOR inhibitor sirolimus reduces angymiolipomavolumes. Some reports have shown improvement in lung function with sirolimus in LAM.We report 3 women with LAM, with a rapid decline in lung function and symptoms and who weretreated with sirolimus (AU)

Lymphangioleiomyomatosis treatment with sirolimus.

Lymphangioleiomyomatosis (LAM) is a rare lung disease, that predominantly affects young females and generally progresses to respiratory failure. There is not sufficient evidence to support the routine use of any treatment in LAM. The only treatment for severe LAM is currently lung transplantation. Activation of mammalian target of rapamycin (mTOR) signalling pathway has been observed in LAM. LAM is often associated with angiomyolipoma in the kidneys. mTOR inhibitor sirolimus reduces angymiolipoma volumes. Some reports have shown improvement in lung function with sirolimus in LAM. We report 3 women with LAM, with a rapid decline in lung function and symptoms and who were treated with sirolimus.

Prolonged travel and venous thromboembolism findings from the RIETE registry.

There is a lack of information on clinical risk factors for venous thromboembolism (VTE) development following prolonged traveling. Clinical characteristics and additional risk factors for VTE in travelers were analyzed in RIETE, an ongoing registry of patients with symptomatic, confirmed acute VTE. Of 26,172 patients enrolled in RIETE as of May 2009, 2% developed VTE in association with recent traveling. Travelers were ten years younger, had significantly more previous VTE events (20% vs. 16%; OR: 1.4; 95%CI: 1.1-1.7) and their body mass index (BMI) was 28.4±5.1 vs. 27.7±5.2 in other patients from the registry (P=0.004). 115 (20%) of recent travelers had previous VTE compared to 16% among others patients (OR: 1.4; 95%CI: 1.1-1.7). Recent travelers used hormones significantly more frequently (8.7% vs. 3.7%; OR: 2.5; 95% CI: 1.8-3.3) and more often had a positive thrombophilia test (16% vs. 8.7%; OR: 2; 95%CI: 1.6-2.6). Travelers used LMWH prophylaxis significantly less frequently than other patients in the registry (2.4% vs. 13%; OR 0.2; 95%CI: 0.1-0.3). There were differences in VTE risk in professional drivers compared to passengers. The current study demonstrates four risk factors for VTE development after long traveling: high BMI, previous VTE, hormone use and thrombophilia. Studies of prophylactic antithrombotic therapy in high risk travelers are warranted.

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry.

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.