Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis

Background: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. Methods: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. Findings: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93–1·06) and a hazard ratio of 1·01 (95% CI 0·96–1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47–0·71) for venous thromboembolism, 1·27 (0·92–1·74) for major bleeding, and 1·34 (1·19–1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42–0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. Interpretation: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. Funding: Canadian Institutes of Health Research

Adhesions and pain in women with first diagnosis of endometriosis: Results from a cross-sectional study

OBJECTIVE: To analyze the relationship between pain and presence, site, and type of adhesions in women with endometriosis. METHODS: This was a multicenter, observational cross-sectional study. Eligible for the Study were women with endometriosis and pelvic pain, consecutively observed during the study period at the collaborating centers. A total of 574 women entered the study. RESULTS: Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in women with endometriosis at stage I-II (65%) and higher in women with stage III-IV (88%); this difference was statistically significant (p <.01). The frequency of adhesions was lower in women with ovarian endometriosis (74%) and higher in those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p <.01). The presence of: adhesions was associated with higher mean visual analog scale (VAS) scores and median multidimensional scale ratings in women with ovarian disease and with stage I-II disease. Women with ovarian adhesions reported higher VAS and multidimensional scale scores (p <.05) than women with peritoneal adhesions or adhesions in other sites. CONCLUSIONS: The results of this study suggest that there is no overall association between the presence of adhesions and the degree of pain in women with endometriosis. The data suggests that there may be an association between adhesions and pain in women with ovarian and Type I-II endometriosis. However, these associations were no longer significant after correction for multiple comparisons. Further research is indicated to test these associations

Adhesions and pain in women with first diagnosis of endometriosis : results from a cross-sectional study

OBJECTIVE: To analyze the relationship between pain and presence, site, and type of adhesions in women with endometriosis. METHODS: This was a multicenter, observational cross-sectional study. Eligible for the study were women with endometriosis and pelvic pain, consecutively observed during the study period at the collaborating centers. A total of 574 women entered the study. RESULTS: Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in women with endometriosis at stage I-II (65%) and higher in women with stage III-IV (88%); this difference was statistically significant (p <.01). The frequency of adhesions was lower in women with ovarian endometriosis (74%) and higher in those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p <.01). The presence of adhesions was associated with higher mean visual analog scale (VAS) scores and median multidimensional scale ratings in women with ovarian disease and with stage I-II disease. Women with ovarian adhesions reported higher VAS and multidimensional scale scores (p <.05) than women with peritoneal adhesions or adhesions in other sites. CONCLUSIONS: The results of this study suggest that there is no overall association between the presence of adhesions and the degree of pain in women with endometriosis. The data suggests that there may be an association between adhesions and pain in women with ovarian and Type I-II endometriosis. However, these associations were no longer significant after correction for multiple comparisons. Further research is indicated to test these associations