Evaluation framework study assessing the role, applicability and adherence to good practice of planning support tools for allocation of development aid for health in low-income and middle-income countries.

OBJECTIVES: Allocation of development aid for health is controversial and challenging. In recent years, several planning-software tools have promised to help decision-makers align resource allocation with their objectives, more clearly connect prioritisation to evidence and local circumstances, and increase transparency and comparability. We aim to explore these tools to provide insight into their fitness for purpose and suggest future directions to fulfil that promise. DESIGN: We identified seven tools that met the inclusion criteria and developed an evaluation framework to compare them along two dimensions for assessing fitness for purpose: ability to produce analyses adhering to principles laid out in the International Decisions Support Initiative (iDSI) Reference Case for health economic evaluations; and resources required, including expertise and time. We extracted information from documentation and tool use and sent this information to tool developers for confirmation. RESULTS: We categorise the tools into evidence-generating ones, evidence-syntheses ones and process support ones. Tools' fitness for purpose varies by the context, technical capacity and time limitation. The tools adhere to several reference case principles but often not to all of them. The source and underlying assumptions of prepopulated data are often opaque. Comparing vertical interventions across diseases and health system strengthening ones remains challenging. CONCLUSIONS: The plethora of tools that aid priority setting in different ways is encouraging. Developers and users should place further emphasis on their ability to produce analyses that adhere to prioritisation principles. Opportunities for further development include using evidence-generating tools and multicriteria decision analysis approaches complimentarily. However, maintaining tool simplicity should also be considered to allow wider access.

Spontaneous Recurrent Pneumothorax during Pregnancy Secondary to Ectopic Deciduosis.

Background Ectopic deciduosis is a benign presence of endometrial tissue outside of the uterus during pregnancy that rarely presents with pleuropulmonary manifestations and recurrent pneumothorax. Case Description We report a 35-year-old woman at 15 weeks' gestation with a history of recurrent intrapartum right pneumothorax found to have pleural, pulmonary, and diaphragmatic lesions and a middle lobe air leak. Wedge resection of the middle lobe and mechanical pleurodesis was performed. Histopathological analysis was progesterone receptor and PAX8 positive consistent with ectopic deciduosis. Conclusion Ectopic deciduosis is a rare cause of recurrent pneumothorax in pregnancy and should be considered when evaluating these patients.

Laparoscopic common bile duct exploration by acute care surgeons saves time and money compared to ERCP.

BACKGROUND: A typical pathway for treatment of choledocholithiasis (CD) in emergency general surgery patients involves same admission laparoscopic cholecystectomy (LC) with either preoperative or postoperative endoscopic retrograde cholangiopancreatography (ERCP). The goal of this study was to describe our initial experience at a safety net hospital with acute care surgeon-performed laparoscopic common bile duct exploration (LCBDE) when CD is confirmed at the time of LC. We hypothesized that this strategy would result in reduced length of stay, and lower charges compared to ERCP. METHODS: This was a retrospective case control study over a 2 year period matching LCBDE to ERCP (1:3) among a cohort of patients with CD confirmed at first procedure. Data is reported as median (interquartile range). Statistical analysis used the Kruskal-Wallis and Chi-squared tests with 95% confidence interval. RESULTS: Demographics, preoperative WBC, and bilirubin were similar between the LCBDE (n = 14) and ERCP (n = 37) groups. Success rate for LCBDE was 11/14 (79%), and the remaining three subjects successfully underwent post-operative ERCP. Overall complication rate for the LCBDE group was 1/14 (7%) and the readmission rate was 0/14 (0%). Length of stay for LCBDE vs ERCP was 2.5 (1-3) vs 5 (3-5) days (p < 0.01). Charges during initial hospitalization was $35858 ($26587-$49570) vs $48662 ($36018-$57106) (p = 0.05). CONCLUSIONS: LCBDE by acute care surgeons at the time of LC was associated with lower charges, reduced hospital length of stay, low rates of post-operative complications, and no readmissions.

Earlier liposomal bupivacaine blocks improve analgesia and decrease opioid requirements for bariatric surgery patients.

INTRODUCTION: Optimal timing of liposomal bupivacaine (LB) transversus abdominis plane (TAP) blocks for bariatric surgery is unknown. We hypothesize that LB TAPs used prior to incision decrease narcotic requirements compared to the completion of surgery. METHODS: Single intuition review of 86 bariatric surgery patients who received LB TAP blocks from 2/2019 through 8/2020. 44 patients received LB at the beginning of the case (Beg) while 42 patients received LB at the completion (End). Morphine equivalent daily doses (MEDD) were compared. RESULTS: MEDD requirements for the Beg-LB group compared to the End-LB group were significantly less on POD 0 (4.8 vs 6.8 MEDD, p = 0.01) and POD 2 (16 vs 32, p = 0.04). Discharge oxycodone prescriptions were lower in the Beg-LB group (15 vs 20, p = 0.008). CONCLUSIONS: Patients who received LB TAP blocks prior to bariatric surgery required fewer narcotics than patients who received the LB TAP at the conclusion of surgery.

The α-globin chain of hemoglobin potentiates tissue plasminogen activator induced hyperfibrinolysis in vitro.

BACKGROUND: Severe injury predisposes patients to trauma-induced coagulopathy, which may be subdivided by the state of fibrinolysis. Systemic hyperfibrinolysis (HF) occurs in approximately 25% of these patients with mortality as high as 70%. Severe injury also causes the release of numerous intracellular proteins, which may affect coagulation, one of which is hemoglobin, and hemoglobin substitutes induce HF in vitro. We hypothesize that the α-globin chain of hemoglobin potentiates HF in vitro by augmenting plasmin activity. METHODS: Proteomic analysis was completed on a pilot study of 30 injured patients before blood component resuscitation, stratified by their state of fibrinolysis, plus 10 healthy controls. Different concentrations of intact hemoglobin A, the α- and ß-globin chains, or normal saline (controls) were added to whole blood, and tissue plasminogen activator (tPA)-challenged thrombelastography was used to assess the degree of fibrinolysis. Interactions with plasminogen (PLG) were evaluated using surface plasmon resonance. Tissue plasminogen activator-induced plasmin activity was evaluated in the presence of the α-globin chain. RESULTS: Only the α- and ß-globin chains increased in HF patients (p < 0.01). The α-globin chain but not hemoglobin A or the ß-globin chain decreased the reaction time and significantly increased lysis time 30 on citrated native thrombelastographies (p < 0.05). The PLG and α-globin chain had interaction kinetics similar to tPA:PLG, and the α-globin chain increased tPA-induced plasmin activity. CONCLUSIONS: The α-globin chain caused HF in vitro by binding to PLG and augmenting plasmin activity and may represent a circulating "moonlighting" mediator released by the tissue damage and hemorrhagic shock inherent to severe injury. LEVEL OF EVIDENCE: Prognostic, level III.

Mental health in the pandemic: a repeated cross-sectional mixed-method study protocol to investigate the mental health impacts of the coronavirus pandemic in the UK.

INTRODUCTION: The WHO declared a global pandemic on 11 March 2020. Since then, the world has been firmly in the grip of the COVID-19. To date, more than 211 730 035 million confirmed cases and more than 4 430 697 million people have died. While controlling the virus and implementing vaccines are the main priorities, the population mental health impacts of the pandemic are expected to be longer term and are less obvious than the physical health ones. Lockdown restrictions, physical distancing, social isolation, as well as the loss of a loved one, working in a frontline capacity and loss of economic security may have negative effects on and increase the mental health challenges in populations around the world. There is a major demand for long-term research examining the mental health experiences and needs of people in order to design adequate policies and interventions for sustained action to respond to individual and population mental health needs both during and after the pandemic. METHODS AND ANALYSIS: This repeated cross-sectional mixed-method study conducts regular self-administered representative surveys, and targeted focus groups and semi-structured interviews with adults in the UK, as well as validation of gathered evidence through citizens' juries for contextualisation (for the UK as a whole and for its four devolved nations) to ensure that emerging mental health problems are identified early on and are properly understood, and that appropriate policies and interventions are developed and implemented across the UK and within devolved contexts. STATA and NVIVO will be used to carry out quantitative and qualitative analysis, respectively. ETHICS AND DISSEMINATION: Ethics approval for this study has been granted by the Cambridge Psychology Research Ethics Committee of the University of Cambridge, UK (PRE 2020.050) and by the Health and Life Sciences Research Ethics Committee of De Montfort University, UK (REF 422991). While unlikely, participants completing the self-administered surveys or participating in the virtual focus groups, semi-structured interviews and citizens' juries might experience distress triggered by questions or conversations. However, appropriate mitigating measures have been adopted and signposting to services and helplines will be available at all times. Furthermore, a dedicated member of staff will also be at hand to debrief following participation in the research and personalised thank-you notes will be sent to everyone taking part in the qualitative research.Study findings will be disseminated in scientific journals, at research conferences, local research symposia and seminars. Evidence-based open access briefings, articles and reports will be available on our study website for everyone to access. Rapid policy briefings targeting issues emerging from the data will also be disseminated to inform policy and practice. These briefings will position the findings within UK public policy and devolved nations policy and socioeconomic contexts in order to develop specific, timely policy recommendations. Additional dissemination will be done through traditional and social media. Our data will be contextualised in view of existing policies, and changes over time as-and-when policies change.

Prospective assessment of fibrinolysis in morbid obesity: tissue plasminogen activator resistance improves after bariatric surgery.

BACKGROUND: Morbid obesity is associated with an increased risk of thrombotic events, which has been attributed to increased thrombotic activity. Multiple mechanisms have been proposed to explain this increased risk, including an inflammatory state with upregulation of procoagulant and antifibrinolytic proteins. We therefore hypothesize that patients with morbid obesity are hypercoagulable and will revert to normal after bariatric surgery. OBJECTIVES: To evaluate changes in the hypercoagulable state after bariatric surgery. SETTING: University Hospital, Bariatric Center of Excellence, United States. METHODS: Thromboelastography (TEG) data were collected on 72 subjects with morbid obesity, with 36 who had 6 months of follow-up after bariatric surgery. TEG data of 75 healthy subjects (HS) without obesity, recent trauma or surgery, acute infection, or chronic conditions (e.g., liver, cardiovascular, or kidney disease; cancer; diabetes; autoimmune or inflammatory disorders; and disorders of coagulation) were used for comparison. TEG was performed alone and with the addition of 75 and 150 ng/mL tissue plasminogen activator (tPA) to quantify fibrinolysis resistance (tPA-challenged TEG). RESULTS: The bariatric surgery cohort had a median age of 40.5 years, a median body mass index of 44.6 kg/m2, and 90% female patients. Median body mass index reduced significantly 6 months post surgery but remained elevated compared with the HS group (31.4 versus 25.4 kg/m2, P < .0001). At 6 months post surgery, subjects had longer reaction time (mean difference, 1.3; P = .02), lower maximum amplitude (-2.4, P = .01), and increased fibrinolysis with low-dose (3.1, P < .0001) and high-dose tPA-challenged TEG (9, P < .0001). Compared with HS, the postsurgery TEG values were still more likely to be abnormal (all P < .05). CONCLUSIONS: Patients with morbid obesity form stronger clots more rapidly and are more resistant to fibrinolysis than subjects without obesity. Bariatric surgery significantly improved the hypercoagulable profile and fibrinolysis resistance of morbid obesity.

Composition of human breast milk in acute kidney injury.

BACKGROUND: Breastfeeding is a widely encouraged practice due to its benefits for mother and the infant. Little is known about the impact of disease states, such as kidney dysfunction and childbirth complications, on the composition of breast milk. METHODS: We describe a case of a 35-year-old woman who suffered a postpartum hemorrhage, was administered a contrast dye prior to computer tomography, and developed an acute kidney injury. Using nuclear magnetic resonance spectrometry, we measured composition of milk in acute kidney injury. The amount of dye secreted into milk was determined using a spectroscopic assay. RESULTS: Here we show that acute kidney injury results in changes in milk composition, but it does not significantly affect major macronutrients. We also determine that iodinated computer tomography contrast dye does not accumulate in milk in appreciable amounts. CONCLUSION: Acute kidney injury has impact on breast milk. Intravenous administration of computer tomography contrast dye does not result in significantly elevated levels in milk.

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin.

BACKGROUND: Hyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy. Recent data demonstrate that red blood cell lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOCs) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy because of the presence of free hemoglobin. MATERIALS AND METHODS: WB was sampled from healthy donors (n = 6). The clotting profile of each citrated sample was evaluated using native thromboelastography. Serial titrations were performed using both HBOC (PolyHeme) and normal saline (NS; 5%, 25%, and 50%) and evaluated both with and without a 75-ng/mL tissue plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin-dependent fibrinolysis. Fibrinolysis was measured and recorded as lysis at 30 min (LY30), the percentage of clot LY30 after maximal clot strength. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman rho coefficients. Groups were also compared using a Friedman test and post hoc analysis with a Bonferroni adjustment. RESULTS: tPA-provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, and 50% titrations: 11%, 21%, and 44%, respectively; Spearman = 0.94; P < 0.001) and NS (11%, 28%, and 58%, respectively; Spearman = 0.790; P < 0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%, 4%, 5%; Spearman = 0.735; P = 0.001) and NS did not (1%, 2%, 1%; r = 0.300; P = 0.186. Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB versus 50% HBOC: 1.8% versus 5.7%, P = 0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC versus 50% HBOC + TXA: 5.6% versus 5.7%, P = 0.92). In addition, the increased fibrinolysis seen with NS was reversed when TXA was present (WB versus 50% NS: 1.8% versus 1.7%, P = 1.0). CONCLUSIONS: HBOCs enhance fibrinolysis both with and without addition of tPA; moreover, this mechanism is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings indicate the hemoglobin molecule or its components stimulate fibrinolysis by both tPA-dependent and innate mechanisms.

Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock.

The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia, and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here, we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma versus normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections.

Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

BACKGROUND: We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline. METHODS: Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis. RESULTS: The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699). CONCLUSION: Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

The "Death Diamond": Rapid thrombelastography identifies lethal hyperfibrinolysis.

BACKGROUND: Postinjury hyperfibrinolysis (HF), defined as LY30 of 3% or greater on rapid thrombelastography (rTEG), is associated with high mortality and large use of blood products. We observed that some cases of HF are reversible and are associated with patients who respond to hemostatic resuscitation; however, other cases of severe HF seem to be associated with these patients' inevitable demise. We therefore sought to define this unsurvivable subtype of HF as a recognizable rTEG tracing pattern. METHODS: We queried our trauma registry for patients who either died or spent at least 1 day in the intensive care unit, received at least 1 U of packed red blood cells, and had an admission rTEG. Within this group of 572 patients, we identified 42 pairs of nonsurvivors and survivors who matched on age, sex, injury mechanism, and New Injury Severity Score (NISS). We inspected the rTEG tracings to ascertain if any pattern was found exclusively within the nonsurviving group and applied these findings to the cohort of 572 patients to assess the predictive value for mortality. RESULTS: Within the matched group, 17% of the patients developed HF. Within the HF subgroup, a unique rTEG pattern was present in 14 HF patients who died and in none of the survivors. This pattern was a "diamond-shaped" tracing with a short time to maximum amplitude of 14 minutes or shorter and complete lysis before the LY30 point. When these criteria are applied to the 572 unmatched patients, this pattern had a 100% positive predictive value for mortality. CONCLUSION: Patients displaying the "death diamond" pattern on their admission rTEG are at higher risk for mortality. Given the volume of blood products and other resources that these patients consume, this thrombelastography pattern may represent an objective criterion to discontinue efforts at hemostatic resuscitation. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Sequence variation in vitamin K epoxide reductase gene is associated with survival and progressive coronary calcification in chronic kidney disease.

OBJECTIVE: Sequence variations in the gene(s) encoding vitamin K epoxide reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been associated with increased cardiovascular disease in the general population. Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC genotype would be associated with mortality and progression of CAC ≤ 4 years. APPROACH AND RESULTS: This study is an observational, prospective study of 167 individuals with stages 3 to 5 chronic kidney disease. Survival ≤ 4 years was assessed in all participants, and CAC progression was measured in a subset of 86 patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4-year CAC score, those with the CG/GG genotype had an increased risk of progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular filtration rate, and hypertension) compared with those with the CC genotype. Four-year mortality risk was 4 times higher for individuals with the CG/GG genotypes compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence interval, 1.2-12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated glomerular filtration rate, baseline CAC, and hypertension. CONCLUSIONS: Patients with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a poorer survival. These data provide new perspectives on the potential extrahepatic role of VKORC1 in individuals with chronic kidney disease.

Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease.

BACKGROUND: Epicardial fat, quantified in a single multi-slice computed tomography (MSCT) slice, is a reliable estimate of total epicardial fat volume (EFV). We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV) in pre-dialysis chronic kidney disease (CKD) patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC). METHODS: 94 pre-dialysis stage 3-5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected. RESULTS: Mean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m2. Mean ssEFV was 5.03 ± 2.4 cm3. By univariate analysis, body mass index (BMI) (r = 0.53; P = <0.0001), abdominal obesity (r = 0.51; P < 0.0001), high density lipoprotein (HDL) cholesterol (r = - 0.39; P = <0.0001), insulin resistance (log homeostasis model assessment of insulin resistance (log HOMA-IR)) (r = 0.38, P = 0.001), log interleukin-6 (IL-6) (r = 0.34; P = 0.001), and log urinary albumin to creatinine ratio (UACR) (r = 0.30, P = 0.004) demonstrated the strongest associations with ssEFV. Log coronary artery calcification (log CAC score) (r = 0.28, P = 0.006), and log fibroblast growth factor-23 (log FGF-23) (r = 0.23, P = 0.03) were also correlated with ssEFV. By linear regression, log CAC score (beta =0.40; 95% confidence interval (CI), 0.01-0.80; P = 0.045), increasing levels of IL-6 (beta = 0.99; 95% CI, 0.38 - 1.61; P = 0.002), abdominal obesity (beta = 1.86; 95% CI, 0.94 - 2.8; P < 0.0001), lower HDL cholesterol (beta = -2.30; 95% CI, - 3.68 to -0.83; P = 0.002) and albuminuria (log UACR, beta = 0.81; 95% CI, 0.2 to 1.4; P = 0.01) were risk factors for increased ssEFV. CONCLUSIONS: In stage 3-5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

Revisiting early postinjury mortality: are they bleeding because they are dying or dying because they are bleeding?

BACKGROUND: Intense debate continues in the search of the optimal ratio of blood components to deliver preemptively in the critically injured patient anticipated to require a massive transfusion. A major challenge is distinguishing patients with refractory coagulopathy versus those with overwhelming injuries who will perish irrespective of blood component administration. The hypothesis of this clinical study is that a predominant number of early deaths from hemorrhage are irretrievable despite an aggressive transfusion policy. MATERIALS AND METHODS: During the 7-y period ending in December 2009, there were 772 in-hospital trauma deaths. Each of these deaths had been assigned a cause of death via concurrent review by the multidisciplinary hospital trauma quality improvement committee. Emergency department deaths and patients arriving from outside facilities were excluded from this study. RESULTS: Of the 382 patients (49.5% of total) who died secondary to acute blood loss, 84 (22.0%) survived beyond the ED; of these 84, 68 (81%) were male, mean age was 31 y, and 30 (36%) sustained blunt trauma. Cause of death was determined to be exsanguination in 63 (75%), coagulopathy in 13 (15%), metabolic failure in 5 (6%), and indeterminate in 3 patients (4%). CONCLUSION: These data indicate that 75% of patients who succumb to postinjury acute blood loss are bleeding because they are dying rather than dying because they are bleeding. Conversely, only 13 (2%) of the hospital deaths were attributed to refractory coagulopathy. These critical facts need to be considered in designing studies to determine optimal massive transfusion protocols.

Fat-soluble vitamins in advanced CKD/ESKD: a review.

Patients requiring dialysis often experience a significant decline in their nutritional status through a combination of chronic disease, reduced appetite, and dietary restrictions, which places them at risk for vitamin deficiencies. The concept of vitamin deficiency has evolved from obvious deficiency states to the subtle effects that suboptimal intake may have on chronic disease prevalence or progression. The purpose of this study was to summarize the current state of knowledge regarding the status of the fat-soluble vitamins (A, D, E, and K) in patients with chronic kidney disease receiving hemodialysis.

Statins are associated with a reduced risk of bone fracture in hemodialysis (HD) patients.

The Dialysis Outcomes and Practice Patterns Study reported a statistically non-significant protective effect of HMG-co reductase inhibitors (statins) on bone fracture risk in hemodialysis (HD) patients. We sought to determine whether statin exposure was associated with reduced risk of bone fracture in our HD population. This was a retrospective cohort study of 174 prevalent HD patients. Fracture data are abstracted from the medical record. Subjects were considered to be on a statin if they were exposed at any time since the date of dialysis initiation. The subjects were 174 HD patients (68.4% male) with a median age of 69.1 and age range from 25.2 to 96.3 years. The median age at initiation of HD was 62.5, ranging from 15.2 to 90.5 years. The mean (SD) dialysis vintage was 7.3 (4.5) years. Seventy-seven subjects (44.3%) had statin exposure. There were a total of 54 first bone fractures. There was a positive correlation between bone fracture and dialysis vintage (p=0.023) and a negative association between bone fracture and statin exposure (p=0.044). Those with statin exposure had a higher prevalence of CAD (p=0.030) compared with those not exposed. Logistic regression analysis (stepwise, alpha=0.05) was performed with dependent variable bone fracture and independent variables age at HD initiation (forced), dialysis vintage, gender (forced), prednisone use (forced), and statin exposure. The significant predictors of bone fracture (R2=0.14, p=0.004) were age at HD initiation (p=0.016), dialysis vintage (p=0.007), and absence of statin exposure (p=0.019). Statin exposure appears to be associated with a reduced frequency of bone fracture in HD patients. Future studies evaluating the potential anabolic effect of statins on bone are required.

Apolipoprotein(a) phenotype and lipoprotein(a) level predict peritoneal dialysis patient mortality.

OBJECTIVE: To examine the associations between lipoprotein(a) [Lp(a)] level, apolipoprotein(a) [apo(a)] phenotype, and patient mortality in peritoneal dialysis (PD) patients. DESIGN: Observational prospective study of prevalent PD patients. SETTING: Tertiary-care health sciences center. PATIENTS: 54 prevalent PD patients were followed prospectively for 24 months. MAIN OUTCOME MEASURES: The exposures were Lp(a) level and apo(a) phenotype, designated by the apo(a) isoform size (number of kringle 4 repeats). Outcome was death from any cause. RESULTS: There were 24 deaths in 77.9 patient-years' follow-up. The independent predictors of death in the multivariate survival analysis were age [relative risk (RR) = 1.03, p = 0.23], diabetes (RR = 3.00, p = 0.03), diastolic blood pressure < or = 70 mmHg (RR = 2.94, p = 0.03), serum albumin (RR = 0.87, p < 0.01), and Lp(a) level (RR = 1.004, p < 0.01). There was strong inverse correlation of Lp(a) with apo(a) isoform size (r = -0.62, p < 0.01). With Lp(a) removed from the model, apo(a) isoform size was a significant predictor of death (RR = 0.91, p = 0.0497). CONCLUSIONS: Lipoprotein(a) level and apo(a) phenotype are associated with PD patient mortality. Measurement of Lp(a) level and apo(a) phenotype may be useful in clinical practice to identify patients at high risk for cardiovascular disease. Large prospective studies are needed to determine if a reversal of the increase in Lp(a) level associated with renal disease and dialysis is feasible and beneficial in reducing the risk of cardiovascular disease and mortality.