Postpartum Hemorrhage in Women with von Willebrand Disease: Consider Other Etiologies.

OBJECTIVE: Higher rates of postpartum hemorrhage (PPH) have been reported for women with von Willebrand disease (VWD). Comprehensive multidisciplinary care reduces these rates; thus PPH may not be secondary to VWD. METHODS: We conducted a retrospective review for the period of 2009-2018, including all VWD pregnancies at 2 tertiary care academic hospitals to determine rates, etiology, and timing of PPH. RESULTS: A total of 63 women with 80 pregnancies were included. Three women had twin pregnancies. Sixty-six pregnancies (82.5%) involved type 1 VWD; 4 (5.0%), type 2 (unclear subtype); 3 (3.8%) type 2A; 3 (3.8%) type 2B; and 2 (2.5%), type 2M. Median age of patients was 32.9 years (range 19-43 y). Most patients were blood type O (65%), and 33 of 80 pregnancies (41.3%) were nulliparous. The mean bleeding assessment score was 8 (range 0-16). Thirty-seven pregnancies (46.3%) received prophylactic hemostatic treatment prior to delivery. Seventy-four percent of pregnancies were delivered vaginally, and 88% received epidural anaesthesia. The majority of pregnancies (78.8%) had von Willebrand factor (VWF) levels assessed during the third trimester, with most (71.3%) achieving VWF levels above 1.00 IU/mL. Four pregnancies (5.2%) were complicated by primary PPH; uterine atony in 2 and placenta previa in 1. Delayed postpartum bleeding occurred in 5 pregnancies (6.3%). CONCLUSION: Multidisciplinary care of pregnancies with VWD improves outcomes. Rates of primary and delayed PPH in this study are lower than previously described and are similar to those of women without VWD. In women with VWD, uterine etiologies for primary PPH need to be considered, in a manner similar to the assessment of women without VWD, to ensure hemostasis is achieved.

The multiple meanings of omnivory influence empirical, modular theory and whole food web stability relationships.

The persistence of whole communities hinges on the presence of select interactions which act to stabilize communities making the identification of these keystone interactions critical. One potential candidate is omnivory, yet theoretical research on omnivory thus far has been dominated by a modular theory approach whereby an omnivore and consumer compete for a shared resource. Empirical research, however, has highlighted the presence of a broader suite of omnivory modules. Here, we integrate empirical data analysis and mathematical models to explore the influence of both omnivory module (including classic, multi-resource, higher level, mutual predation and cannibalism) and omnivore-resource interaction type on food web stability. We use six classic empirical food webs to examine the prevalence of the different types of omnivory, a multi-species consumer-resource model to determine the stability of these different kinds of omnivory within a module context, and finally extend these models to a 50 species, whole food web model to examine the influence of omnivory on whole food web persistence. Our results challenge the concept that omnivory is broadly stabilizing. In particular, we demonstrate that the impact of omnivory depends on the type of omnivory being examined with multi-resource omnivory having the largest correlation with whole food web persistence. Moreover, our results highlight that we need to exercise caution when scaling modular theory to whole food web theory. Cannibalism, for example, was the most persistent and stable omnivory module in the modular theory analysis, but only demonstrated a weak correlation with whole food web persistence. Lastly, our results demonstrate that the frequency of omnivory modules are more important for whole food web persistence than the frequency of omnivore-resource interactions. Together, these results demonstrate that the role of omnivory often depends both on the type of omnivory being examined and the food web within which it is nested. In whole food web models, omnivory acts less as a keystone interaction, rather, specific types of omnivory, particularly multi-resource omnivory, act as keystone modules. Future work integrating module and whole food web theory is critical for resolving the role of key interactions in food webs.

Management of anticoagulation in patients with metastatic castration-resistant prostate cancer receiving abiraterone + prednisone.

PURPOSE: Abiraterone has been proven to be an effective agent used in the management of metastatic castration-resistant prostate cancer, significantly improving overall and progression-free survival. Due to the pharmacodynamic and pharmacokinetic properties of abiraterone, concurrent use with anticoagulation may pose a challenge for clinicians. Thrombosis within the cancer setting continues to increase patient mortality; therefore, appropriate anticoagulation through the use of a management algorithm can reduce adverse events and increase quality of life. METHODS: A review of the literature was preformed by a medical oncologist, haematologist and pharmacists to identify relevant randomized controlled trials, meta-analyses and retrospective studies. Major society guidelines were reviewed to further aid in developing the anticoagulation protocol for non-valvular atrial fibrillation and venous thromboembolism within this patient population. After reviewing the literature, a clinical framework was designed to aid clinicians in the management of those patients receiving abiraterone concurrently with an anticoagulant. RESULTS: In this review, we describe the potential interactions between abiraterone and various anticoagulants and provide management strategies based on the most recent literature for atrial fibrillation, venous thromboembolism and mechanical heart valves to avoid potential drug-drug interactions. CONCLUSION: Abiraterone therapy has become a mainstay of the management of advanced prostate cancer and is often used over prolonged years. In this review, we have summarized a framework of how to use abiraterone in men with prostate cancer on anticoagulants. Evidence available to date suggests that patients with an indication for anticoagulation such as atrial fibrillation, venous thromboembolism and mechanical heart valves can be treated safely with abiraterone in the appropriate setting, with appropriate monitoring.

Is anemia an independent risk factor for postpartum depression in women who have a cesarean section? - A prospective observational study.

BACKGROUND: The symptoms of anemia and depression are very similar suggesting that there may be an association between the two entities. The aim of this study is to assess whether postpartum anemia (PPA) is an independent risk factor for de novo postpartum depression (PPD)in women undergoing elective cesarean section. METHODS: Women after an uncomplicated term cesarean section were recruited and their hemoglobin and iron status were measured on day 3-5 post section and again at 6 weeks. Postpartum depression was screened using the Edinburgh Postnatal Depression Scale (EPDS) and functional capacity was assessed with the RAND 12-item Health survey. RESULTS: One hundred and three women completed the study. The incidence of probable postpartum depression (PPD) as defined by EPDS score ≥ 10 was 17% at 6 weeks. There was no difference in hemoglobin or iron status in women who had PPD compared to those without (OR-0.69; 95% CI-0.15-2.49). Similarly, there was no significant association between low hemoglobin and maternal functional status (OR -1.03; 95% CI-0.34 - 2.94). CONCLUSIONS: Neither anemia or low iron stores were found to be an independent risk factors for postpartum depression or decreased postpartum functional capacity in women who undergo an elective cesarean section.

The Approach to Peripartum Management of Anticoagulation: A Multidisciplinary Survey.

OBJECTIVE: This study sought to determine whether there is practice variation in the treatment and prevention of acute venous thromboembolism (VTE) in pregnant patients, potentially to prioritize future studies. BACKGROUND: The risk of VTE during pregnancy is five-fold that of the non-pregnant state. Guidance is often lacking for the treatment and prophylaxis of VTE because there are few RCTs. METHODS: The study used a cross-sectional study design using a self-administered electronic questionnaire consisting of 11 case scenarios that were sent to hematologists, maternal-fetal medicine specialists, obstetricians and gynaecologists, and internal medicine specialists across Canada. RESULTS: A total of 254 participants responded to the survey and 193 (76%) completed the survey, 158 of whom indicated that they were involved in the decision to anticoagulate these patients. Anticoagulation of patients with superficial venous thrombosis during pregnancy, monitoring of low-molecular-weight heparin antepartum, and discontinuation of this agent at the time of delivery were the scenarios associated with the largest variability of responses. For the management of acute VTE antepartum, most participants favoured a once-daily regimen, although internists more so than obstetrics and gynaecology physicians (94.7% vs. 73.7%). Cesarean section was not perceived to be a procedure with a marked increased risk of thrombosis to warrant thromboprophylaxis because most physicians elected not to offer thromboprophylaxis for this scenario. However, obesity and severe preeclampsia with Cesarean section led to the predominant use of thromboprophylaxis, at 80.0% and 68.4%, respectively. CONCLUSION: Prospective studies addressing peripartum management where significant discrepancies exist are warranted.

The effect of chronotherapy on delirium in critical care - a systematic review.

BACKGROUND: Delirium is highly prevalent within critical care and is linked to adverse clinical outcomes, increased mortality and impaired quality of life. Development of delirium is thought to be caused by multiple risk factors, including disruption of the circadian rhythm. Chronotherapeutic interventions, such as light therapy, music and use of eye shades, have been suggested as an option to improve circadian rhythm within intensive care units. AIM: This review aims to answer the question: Can chronotherapy reduce the prevalence of delirium in adult patients in critical care? DESIGN: This study is a systematic review of quantitative studies. RESEARCH METHOD: Six major electronic databases were searched, and a hand search was undertaken using selected key search terms. Research quality was assessed using the critical appraisal skills programme tools. The studies were critically appraised by both authors independently, and data were extracted. Four themes addressing the research question were identified and critically evaluated. FINDINGS: Six primary research articles that investigated different methods of chronotherapy were identified, and the results suggest that multi-component non-pharmacological interventions are the most effective for reducing the prevalence of delirium in critical care. The melatonergic agonist Ramelteon demonstrated statistically significant reductions in delirium; however, the reliability of the results in answering the review question was limited by the research design. The use of bright light therapy (BLT) and dynamic light application had mixed results, with issues with the research design and outcomes measured limiting the validity of the findings. CONCLUSION: Multi-component non-pharmacological interventions, such as noise and light control, can reduce delirium in critical care, whereas other interventions, such as BLT, have mixed outcomes. Melatonin, as a drug, may be a useful alternative to sedative-hypnotics. RELEVANCE TO CLINICAL PRACTICE: Chronotherapy can reduce the incidence of delirium within critical care, although further research is warranted. Staff education is essential in the implementation of chronotherapy.

Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.

Importance: Antithrombotic medications are among the most commonly prescribed medications. Objective: To characterize rates of hematuria-related complications among patients taking antithrombotic medications. Design, Setting, and Participants: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. Exposures: Receipt of an oral anticoagulant or antiplatelet medication. Main Outcomes and Measures: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. Results: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92). Conclusions and Relevance: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).

Therapeutic hypothermia in patients following traumatic brain injury: a systematic review.

BACKGROUND: The efficacy of therapeutic hypothermia in adult patients with traumatic brain injury is not fully understood. The historical use of therapeutic hypothermia at extreme temperatures was associated with severe complications and led to it being discredited. Positive results from animal studies using milder temperatures led to renewed interest. However, recent studies have not convincingly demonstrated the beneficial effects of therapeutic hypothermia in practice. AIM: This review aims to answer the question: in adults with a severe traumatic brain injury (TBI), does the use of therapeutic hypothermia compared with normothermia affect neurological outcome? DESIGN: Systematic review. METHOD: Four major electronic databases were searched, and a hand search was undertaken using selected key search terms. Inclusion and exclusion criteria were applied. The studies were appraised using a systematic approach, and four themes addressing the research question were identified and critically evaluated. RESULTS: A total of eight peer-reviewed studies were found, and the results show there is some evidence that therapeutic hypothermia may be effective in improving neurological outcome in adult patients with traumatic brain injury. However, the majority of the trials report conflicting results. Therapeutic hypothermia is reported to be effective at lowering intracranial pressure; however, its efficacy in improving neurological outcome is not fully demonstrated. This review suggests that therapeutic hypothermia had increased benefits in patients with haematoma-type injuries as opposed to those with diffuse injury and contusions. It also suggests that cooling should recommence if rebound intracranial hypertension is observed. CONCLUSION: Although the data indicates a trend towards better neurological outcome and reduced mortality rates, higher quality multi-centred randomized controlled trials are required before therapeutic hypothermia is implemented as a standard adjuvant therapy for treating traumatic brain injury. RELEVANCE TO CLINICAL PRACTICE: Therapeutic hypothermia can have a positive impact on patient outcome, but more research is required.

Ecological Implications of Steady State and Nonsteady State Bioaccumulation Models.

Accurate predictions on the bioaccumulation of persistent organic pollutants (POPs) are critical for hazard and ecosystem health assessments. Aquatic systems are influenced by multiple stressors including climate change and species invasions and it is important to be able to predict variability in POP concentrations in changing environments. Current steady state bioaccumulation models simplify POP bioaccumulation dynamics, assuming that pollutant uptake and elimination processes become balanced over an organism's lifespan. These models do not consider the complexity of dynamic variables such as temperature and growth rates which are known to have the potential to regulate bioaccumulation in aquatic organisms. We contrast a steady state (SS) bioaccumulation model with a dynamic nonsteady state (NSS) model and a no elimination (NE) model. We demonstrate that both the NSS and the NE models are superior at predicting both average concentrations as well as variation in POPs among individuals. This comparison demonstrates that temporal drivers, such as environmental fluctuations in temperature, growth dynamics, and modified food-web structure strongly determine contaminant concentrations and variability in a changing environment. These results support the recommendation of the future development of more dynamic, nonsteady state bioaccumulation models to predict hazard and risk assessments in the Anthropocene.

Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.

BACKGROUND: Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. METHODS: In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. FINDINGS: Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01). INTERPRETATION: Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.

Synergistic interactions of biotic and abiotic environmental stressors on gene expression.

Understanding the response of organisms to multiple stressors is critical for predicting if populations can adapt to rapid environmental change. Natural and anthropogenic stressors often interact, complicating general predictions. In this study, we examined the interactive and cumulative effects of two common environmental stressors, lowered calcium concentration, an anthropogenic stressor, and predator presence, a natural stressor, on the water flea Daphnia pulex. We analyzed expression changes of five genes involved in calcium homeostasis - cuticle proteins (Cutie, Icp2), calbindin (Calb), and calcium pump and channel (Serca and Ip3R) - using real-time quantitative PCR (RT-qPCR) in a full factorial experiment. We observed strong synergistic interactions between low calcium concentration and predator presence. While the Ip3R gene was not affected by the stressors, the other four genes were affected in their transcriptional levels by the combination of the stressors. Transcriptional patterns of genes that code for cuticle proteins (Cutie and Icp2) and a sarcoplasmic calcium pump (Serca) only responded to the combination of stressors, changing their relative expression levels in a synergistic response, while a calcium-binding protein (Calb) responded to low calcium stress and the combination of both stressors. The expression pattern of these genes (Cutie, Icp2, and Serca) were nonlinear, yet they were dose dependent across the calcium gradient. Multiple stressors can have complex, often unexpected effects on ecosystems. This study demonstrates that the dominant interaction for the set of tested genes appears to be synergism. We argue that gene expression patterns can be used to understand and predict the type of interaction expected when organisms are exposed simultaneously to natural and anthropogenic stressors.

PCB Food Web Dynamics Quantify Nutrient and Energy Flow in Aquatic Ecosystems.

Measuring in situ nutrient and energy flows in spatially and temporally complex aquatic ecosystems represents a major ecological challenge. Food web structure, energy and nutrient budgets are difficult to measure, and it is becoming more important to quantify both energy and nutrient flow to determine how food web processes and structure are being modified by multiple stressors. We propose that polychlorinated biphenyl (PCB) congeners represent an ideal tracer to quantify in situ energy and nutrient flow between trophic levels. Here, we demonstrate how an understanding of PCB congener bioaccumulation dynamics provides multiple direct measurements of energy and nutrient flow in aquatic food webs. To demonstrate this novel approach, we quantified nitrogen (N), phosphorus (P) and caloric turnover rates for Lake Huron lake trout, and reveal how these processes are regulated by both growth rate and fish life history. Although minimal nutrient recycling was observed in young growing fish, slow growing, older lake trout (>5 yr) recycled an average of 482 Tonnes·yr(-1) of N, 45 Tonnes·yr(-1) of P and assimilated 22 TJ yr(-1) of energy. Compared to total P loading rates of 590 Tonnes·yr(-1), the recycling of primarily bioavailable nutrients by fish plays an important role regulating the nutrient states of oligotrophic lakes.

A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia.

The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).

Effect of season and habitat on PCB bioaccumulation by caged bluegill sunfish deployed in a Great Lakes area of concern.

Bluegill sunfish were caged in the Detroit River, Ontario, Canada, for 64 days to determine bioaccumulation rates of PCBs. Deployments involved placing fish in cages suspended in the water (suspended cages) compared to cages partially buried in sediments. Deployments were performed in the summer and winter months. During summer, fish exhibited significant increases in body weight and lipid content (sediment associated cages only), whereas in winter, body weights did not change. Lipid normalized PCB concentrations and PCB mass in fish increased significantly with time in summer deployments, but not in winter. Fish continued to accumulate PCBs over the 64 days caging duration except for PCBs 33, 49, and 52 in sediment associated cages. There were no significant differences in the bioaccumulation of PCBs between cage types. This study confirms that biomonitoring studies using caged fish should ensure chemical toxicokinetics are consistent when comparing bioaccumulation results among sites and/or time points.

Antithrombotic therapy for improving maternal or infant health outcomes in women considered at risk of placental dysfunction.

BACKGROUND: Pregnancy complications such as pre-eclampsia and eclampsia, intrauterine growth restriction and placental abruption are thought to have a common origin related to abnormalities in the development and function of the placenta. OBJECTIVES: To compare, using the best available evidence, the benefits and harms of antenatal antithrombotic therapy to improve maternal or infant health outcomes in women considered at risk of placental dysfunction, when compared with other treatments, placebo or no treatment. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 July 2012). SELECTION CRITERIA: Randomised controlled trials comparing antenatal antithrombotic therapy (either alone or in combination with other agents) with placebo or no treatment, or any other treatment in the antenatal period to improve maternal or infant health outcomes in women considered at risk of placental dysfunction. DATA COLLECTION AND ANALYSIS: Two review authors evaluated trials under consideration for appropriateness for inclusion and methodological quality without consideration of their results according to the prestated eligibility criteria. We used a fixed-effect meta-analysis for combining study data if the trials were judged to be sufficiently similar. We investigated heterogeneity by calculating I² statistic, and if this indicated a high level of heterogeneity among the trials included, we used a random-effects model. MAIN RESULTS: Our search strategy identified 18 reports of 14 studies for consideration. The original review included five studies (484 women) which met the inclusion criteria, with a further five studies included in the updated review, involving an additional 655 women. The overall quality of the included trials was considered fair to good.Nine studies compared heparin (alone or in combination with dipyridamole or low-dose aspirin) with no treatment; and one compared trapidil (triazolopyrimidine).While this review identified the use of heparin to be associated with a statistically significant reduction in risk of perinatal mortality (six studies; 653 women; risk ratio (RR) 0.40; 95% confidence intervals (CI) 0.20 to 0.78), preterm birth before 34 (three studies; 494 women; RR 0.46; 95% CI 0.29 to 0.73) and 37 (five studies; 621 women; RR 0.72; 95% CI 0.58 to 0.90) weeks' gestation, and infant birthweight below the 10th centile for gestational age (seven studies; 710 infants; RR 0.41; 95% CI 0.27 to 0.61), there is a lack of reliable information available related to clinically relevant, serious adverse infant health outcomes, which have not been reported to date. AUTHORS' CONCLUSIONS: While treatment with heparin for women considered to be at particularly high risk of adverse pregnancy complications secondary to placental insufficiency was associated with a statistically significant reduction in risk of perinatal mortality, preterm birth before 34 and 37 weeks' gestation, and infant birthweight below the 10th centile for gestational age when compared with no treatment for women considered at increased risk of placental dysfunction, to date, important information about serious adverse infant and long-term childhood outcomes is unavailable.

Helping individuals obtain health coverage under the ACA.

Hospitals should consider adopting eight strategies for helping individuals obtain health coverage: Design enrollment procedures and practices that are transparent, consistent, and supported by effective tools. Determine optimal levels of staffing and support for eligibility and enrollment functions. Educate patients on health coverage options. Position trained staff at critical access points. Use innovative strategies to reach vulnerable populations. Partner with key external stakeholders. Partner with service vendors. Assess the new environment.

VTE prophylaxis in pregnant people with chronic physical disability: Data from a physicians survey and the need for guidance.

Background: International guidelines recommend risk assessment during the antepartum and postpartum period to inform VTE prophylaxis. We aimed to evaluate physicians' approach to VTE prophylaxis of women with chronic physical disability (CPD) during pregnancy. Methods: A cross-sectional study consisting of a self-administered electronic questionnaire was sent to specialists across Canada. Results: Seventy-three participants responded to the survey, and 55 (75.3%) completed the survey including 33 (60%) Maternal Fetal Medicine (MFM) specialists and 22 (40%) Internal Medicine (IM) specialists including physicians with an interest in Obstetric Medicine. Our study shows considerable variation in VTE thromboprophylaxis during pregnancy with CPD. Most respondents favoured antepartum (67.3%) and postpartum (65.5%) VTE prophylaxis for pregnancies within a year of spinal cord injury. Conclusions: In order to better manage this complex population, CPD should be considered as a risk factor for development of VTE.

Health Experiences of Nurses during the COVID-19 Pandemic: A Mixed Methods Study.

This study characterizes the impact of the COVID-19 pandemic on the mental and physical health of nurses. Qualitative data (collected using semi-structured interviews) were integrated with quantitative data (collected concurrently using the SF-12 Health Survey). Nurses (N = 30) compared their health prior to and during the first pandemic wave (March-May 2020). Interviews were analyzed thematically; descriptive statistics and t-tests compared pre-pandemic to current SF-12 scores. Qualitative findings demonstrated an impact on nurses' mental health expressed as isolation, loss, intense emotions, and feelings of being expendable. Impact on nurses' physical health included exhaustion, personal protective equipment skin breakdown, limited breaks from work, and virus exposure. Quantitative results show nurses' experienced declines in overall mental health (p < .001), and multiple physical health domains: role limitations due to physical problems (p < .0001), bodily pain (p < .0001), and general health (p < .0001). Promotion of nurses' well-being and safety, as well as education in emergency preparedness, must be given precedence to protect nurses' health.

Ecological network complexity scales with area.

Larger geographical areas contain more species-an observation raised to a law in ecology. Less explored is whether biodiversity changes are accompanied by a modification of interaction networks. We use data from 32 spatial interaction networks from different ecosystems to analyse how network structure changes with area. We find that basic community structure descriptors (number of species, links and links per species) increase with area following a power law. Yet, the distribution of links per species varies little with area, indicating that the fundamental organization of interactions within networks is conserved. Our null model analyses suggest that the spatial scaling of network structure is determined by factors beyond species richness and the number of links. We demonstrate that biodiversity-area relationships can be extended from species counts to higher levels of network complexity. Therefore, the consequences of anthropogenic habitat destruction may extend from species loss to wider simplification of natural communities.