Association of lifetime lactation and age at natural menopause: a prospective cohort study.

OBJECTIVE: The aim of this study was to examine the association between duration of lifetime lactation and age at natural menopause. METHODS: In this prospective cohort study, we analyzed parous premenopausal women in the multiethnic Study of Women's Health Across the Nation who were followed approximately annually for 10 years (1995-2008). Lifetime lactation was defined as the duration of breastfeeding across all births in months. Age at natural menopause was defined as age in years after 12 consecutive months of amenorrhea after the final menstrual period for no other reported cause. We used Cox proportional hazard models to analyze time to natural menopause with age as the underlying time scale. Multivariable models controlled for education, race/ethnicity, parity, smoking, body mass index, and oral contraceptive use. RESULTS: Among 2,377 women, 52.6% experienced natural menopause during follow-up and reported a valid final menstrual period date. The small, crude association between lifetime lactation up to 24 months and later age at natural menopause attenuated to nonsignificance in adjusted models (6 months: adjusted hazard ratio [AHR], 0.96; 95% confidence interval (CI), 0.87-1.06; 12 months: AHR, 0.95; 95% CI, 0.82-1.11; 18 months: AHR, 0.96; 95% CI, 0.82-1.13; 24 months: AHR, 0.99; 95% CI, 0.84-1.16). CONCLUSIONS: Duration of lifetime lactation was not associated with age at natural menopause after controlling for sociodemographic characteristics.

Variation in use of damage control laparotomy for trauma by trauma centers in the United States, Canada, and Australasia.

BACKGROUND: It is unknown how frequently damage control (DC) laparotomy is used across trauma centers in different countries. We conducted a cross-sectional survey of trauma centers in the United States, Canada, and Australasia to study variations in use of the procedure and predictors of more frequent use of DC laparotomy. METHODS: A self-administered, electronic, cross-sectional survey of trauma centers in the United States, Canada, and Australasia was conducted. The survey collected information about trauma center and program characteristics. It also asked how often the trauma program director estimated DC laparotomy was performed on injured patients at that center on average over the last year. Multivariable logistic regression was used to identify predictors of a higher reported frequency of use of DC laparotomy. RESULTS: Of the 366 potentially eligible trauma centers sent the survey, 199 (51.8%) trauma program directors or leaders responded [United States = 156 (78.4%), Canada = 26 (13.1%), and Australasia = 17 (8.5%)]. The reported frequency of use of DC laparotomy was highly variable across trauma centers. DC laparotomy was used more frequently in level-1 than level-2 or -3 trauma centers. Further, high-volume level-1 centers used DC laparotomy significantly more often than lower volume level-1 centers (p = 0.02). Nearly half (48.4%) of high-volume volume level-1 trauma centers reported using the procedure at least once weekly. Significant adjusted predictors of more frequent use of DC laparotomy included country of origin [odds ratio (OR) for the United States vs. Canada = 7.49; 95% confidence interval (CI) 1.39-40.27], level-1 verification status (OR = 6.02; 95% CI 2.01-18.06), and the assessment of a higher number of severely injured (Injury Severity Scale score > 15) patients (OR per-100 patients = 1.62; 95% CI 1.20-2.18) and patients with penetrating injuries (OR per-5% increase = 1.27; 95% CI 1.01-1.58) in the last year. CONCLUSIONS: The reported frequency of use of DC laparotomy was highly variable across trauma centers. Those centers that most need to evaluate the benefit-to-risk ratio of using DC laparotomy in different scenarios may include high-volume, level-1 trauma centers, particularly those that often manage penetrating injuries.

Evidence for use of damage control surgery and damage control interventions in civilian trauma patients: a systematic review.

BACKGROUND: Although damage control (DC) surgery is widely assumed to reduce mortality in critically injured patients, survivors often suffer substantial morbidity, suggesting that it should only be used when indicated. The purpose of this systematic review was to determine which indications for DC have evidence that they are reliable and/or valid (and therefore in which clinical situations evidence supports use of DC or that DC improves outcomes). METHODS: We searched 11 databases (1950-April 1, 2019) for studies that enrolled exclusively civilian trauma patients and reported data on the reliability (consistency of surgical decisions in a given clinical scenario) or content (surgeons would perform DC in that clinical scenario or the indication predicted use of DC in practice), construct (were associated with poor outcomes), or criterion (were associated with improved outcomes when DC was conducted instead of definitive surgery) validity for suggested indications for DC surgery or DC interventions. RESULTS: Among 34,979 citations identified, we included 36 cohort studies and three cross-sectional surveys in the systematic review. Of the 59 unique indications for DC identified, 10 had evidence of content validity [e.g., a major abdominal vascular injury or a packed red blood cell (PRBC) volume exceeding the critical administration threshold], nine had evidence of construct validity (e.g., unstable patients with combined abdominal vascular and pancreas gunshot injuries or an iliac vessel injury and intraoperative acidosis), and six had evidence of criterion validity (e.g., penetrating trauma patients requiring > 10 U PRBCs with an abdominal vascular and multiple abdominal visceral injuries or intraoperative hypothermia, acidosis, or coagulopathy). No studies evaluated the reliability of indications. CONCLUSIONS: Few indications for DC surgery or DC interventions have evidence supporting that they are reliable and/or valid. DC should be used with respect for the uncertainty regarding its effectiveness, and only in circumstances where definitive surgery cannot be entertained.

Correction to: Ethical considerations in conducting surgical research in severe complicated intra-abdominal sepsis.

[This corrects the article DOI: 10.1186/s13017-019-0259-9.].

Challenges and potential solutions to the evaluation, monitoring, and regulation of surgical innovations.

BACKGROUND: As it may be argued that many surgical interventions provide obvious patient benefits, formal, staged assessment of the efficacy and safety of surgical procedures has historically been and remains uncommon. The majority of innovative surgical procedures have therefore often been developed based on anatomical and pathophysiological principles in an attempt to better manage clinical problems. MAIN BODY: In this manuscript, we sought to review and contrast the models for pharmaceutical and surgical innovation in North America, including their stages of development and methods of evaluation, monitoring, and regulation. We also aimed to review the present structure of academic surgery, the role of methodological experts and funding in conducting surgical research, and the current system of regulation of innovative surgical procedures. Finally, we highlight the influence that evidence and surgical history, education, training, and culture have on elective and emergency surgical decision-making. The above discussion is used to support the argument that the model used for assessment of innovative pharmaceuticals cannot be applied to that for evaluating surgical innovations. It is also used to support our position that although the evaluation and monitoring of innovative surgical procedures requires a rigorous, fit-for-purpose, and formal system of assessment to protect patient safety and prevent unexpected adverse health outcomes, it will only succeed if it is supported and championed by surgical practice leaders and respects surgical history, education, training, and culture. CONCLUSION: We conclude the above debate by providing a recommended approach to the evaluation, monitoring, and regulation of surgical innovations, which we hope may be used as a guide for all stakeholders involved in interpreting and/or conducting future surgical research.

Ethical considerations in conducting surgical research in severe complicated intra-abdominal sepsis.

Background: Severe complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS. Main body: Research in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity. Conclusions: A delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm.

A Clinical Risk Prediction Tool for 6-Month Mortality After Dialysis Initiation Among Older Adults.

BACKGROUND: Information on an individual's risk for death following dialysis therapy initiation may inform the decision to initiate maintenance dialysis for older adults. We derived and validated a clinical risk prediction tool for all-cause mortality among older adults during the first 6 months of maintenance dialysis treatment. STUDY DESIGN: Prediction model using retrospective administrative and clinical data. SETTING & PARTICIPANTS: We linked administrative and clinical data to define a cohort of 2,199 older adults (age ≥ 65 years) in Alberta, Canada, who initiated maintenance dialysis therapy (excluding acute kidney injury) in May 2003 to March 2012. CANDIDATE PREDICTORS: Demographics, laboratory data, comorbid conditions, and measures of health system use. OUTCOMES: All-cause mortality within 6 months of dialysis therapy initiation. ANALYTICAL APPROACH: Predicted mortality by logistic regression with 10-fold cross-validation. RESULTS: 375 (17.1%) older adults died within 6 months. We developed a 19-point risk score for 6-month mortality that included age 80 years or older (2 points), glomerular filtration rate of 10 to 14.9mL/min/1.73m2 (1 point) or ≥15mL/min/1.73m2 (3 points), atrial fibrillation (2 points), lymphoma (5 points), congestive heart failure (2 points), hospitalization in the prior 6 months (2 points), and metastatic cancer (3 points). Model discrimination (C statistic = 0.72) and calibration (Hosmer-Lemeshow χ2=10.36; P=0.2) were reasonable. As examples, a score < 5 equated to <25% of individuals dying in 6 months, whereas a score > 12 predicted that more than half the individuals would die in the first 6 months. LIMITATIONS: The tool has not been externally validated; thus, generalizability cannot be assessed. CONCLUSIONS: We used readily available clinical information to derive and internally validate a 7-variable tool to predict early mortality among older adults after dialysis therapy initiation. Following successful external validation, the tool may be useful as a clinical decision tool to aid decision making for older adults with kidney failure.

Opinions of Practicing Surgeons on the Appropriateness of Published Indications for Use of Damage Control Surgery in Trauma Patients: An International Cross-Sectional Survey.

BACKGROUND: Variation in use of damage control (DC) surgery across trauma centers may be partially driven by surgeon uncertainty as to when it is appropriately indicated. We sought to determine opinions of practicing surgeons on the appropriateness of published indications for trauma DC surgery. STUDY DESIGN: We asked 384 trauma centers in the United States, Canada, and Australasia to nominate 1 to 3 surgeons at their center to participate in a survey about DC surgery. We then asked nominated surgeons their opinions on the appropriateness (benefit-to-harm ratio) of 43 literature-derived indications for use of DC surgery in adult civilian trauma patients. RESULTS: In total, 232 (64.8%) trauma centers nominated 366 surgeons, of whom 201 (56.0%) responded. Respondents rated 15 (78.9%) preoperative and 23 (95.8%) intraoperative indications to be appropriate. Indications respondents agreed had the greatest expected benefit included a temperature <34°C, arterial pH <7.2, and laboratory-confirmed (international normalized ratio/prothrombin time and/or partial thromboplastin time >1.5 times normal) or clinically observed coagulopathy in the pre- or intraoperative setting; administration of >10 units of packed red blood cells; requirement for a resuscitative thoracotomy in the emergency department; and identification of a juxtahepatic venous injury or devascularized or destroyed pancreas, duodenum, or pancreaticoduodenal complex during operation. Ratings were consistent across subgroups of surgeons with different training, experience, and practice settings. CONCLUSIONS: We identified 38 indications that practicing surgeons agreed appropriately justified the use of DC surgery. Until further studies become available, these indications constitute a consensus opinion that can be used to guide practice in the current era of changing trauma resuscitation practices.

Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5).

BACKGROUND: Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a ß-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. STRUCTURE OF STUDY: The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis. POWER CALCULATIONS: A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. IMPLICATIONS: This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients.

Indications for Use of Damage Control Surgery in Civilian Trauma Patients: A Content Analysis and Expert Appropriateness Rating Study.

OBJECTIVES: To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients. BACKGROUND: Although DC surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated. METHODS: Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice. RESULTS: The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability. CONCLUSIONS: This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.

Indications for use of thoracic, abdominal, pelvic, and vascular damage control interventions in trauma patients: A content analysis and expert appropriateness rating study.

BACKGROUND: The use of abbreviated or damage control (DC) interventions may improve outcomes in severely injured patients when appropriately indicated. We sought to determine which indications for DC interventions have been most commonly reported in the peer-reviewed literature to date and evaluate the opinions of experts regarding the appropriateness (expected benefit-to-harm ratio) of the reported indications for use in practice. METHODS: Two investigators used an abbreviated grounded theory method to synthesize indications for 16 different DC interventions reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. For each indication code, an international panel of trauma surgery experts (n = 9) then rated the appropriateness of conducting the DC intervention of interest in an adult civilian trauma patient. RESULTS: The 424 indications identified in the literature were synthesized into 101 unique indications. The panel assessed 12 (70.6%) of the coded indications for the 7 different thoracic, 47 (78.3%) for the 7 different abdominal/pelvic, and 18 (75.0%) for the 2 different vascular interventions to be appropriate for use in practice. These included indications for rapid lung-sparing surgery (pneumonorrhaphy, pulmonary tractotomy, and pulmonary wedge resection) (n = 1); pulmonary tractotomy (n = 3); rapid, simultaneously stapled pneumonectomy (n = 1); therapeutic mediastinal and/or pleural space packing (n = 4); temporary thoracic closure (n = 3); therapeutic perihepatic packing (n = 28); staged pancreaticoduodenectomy (n = 2); temporary abdominal closure (n = 12); extraperitoneal pelvic packing (n = 5); balloon catheter tamponade (n = 6); and temporary intravascular shunting (n = 11). CONCLUSION: This study identified a list of candidate appropriate indications for use of 12 different DC interventions that were suggested by authors of peer-reviewed articles and assessed by a panel of independent experts to be appropriate. These indications may be used to focus future research and (in the interim) guide surgical practice while studies are conducted to evaluate their impact on patient outcomes.

Indications for use of damage control surgery and damage control interventions in civilian trauma patients: A scoping review.

BACKGROUND: Variation in the use of damage control (DC) surgery across trauma centers may partially be driven by uncertainty as to when the procedure is indicated. We sought to scope the literature on DC surgery and DC interventions, identify their reported indications, and examine the content and evidence upon which they are based. METHODS: We searched MEDLINE, EMBASE, PubMed, Scopus, Web of Science, and the Cochrane Library (1950-February 14, 2014) and the grey literature for original and nonoriginal citations reporting indications for DC surgery or DC interventions in civilian trauma patients. RESULTS: Among 27,732 citations identified, we included 270 peer-reviewed articles in the scoping review. Of these, 156 (57.8%) represented original research, primarily (75.0%) cohort studies. The articles reported 1,099 indications for DC surgery and 418 indications for 15 different DC interventions. The majority of indications for DC interventions were for abdominal (56.5%) procedures, including therapeutic perihepatic packing (56.5%), temporary abdominal closure/open abdominal management (40.7%), and staged pancreaticoduodenectomy (2.8%). Most DC surgery indications were based on intraoperative findings (71.7%) and represented characteristics of the injured patient (94.5%), including their physiology (57.6%), injuries (38.9%), and/or the amount or type of resuscitation provided (14.3%). Others were dependent on characteristics of the treating surgeon (12.1%), the patient's physiologic response to trauma care (9.6%), and/or the trauma care environment (1.5%). Approximately half (49.5%) included a decision threshold (e.g., pH < X) and, while most (74.7%) were based on a single clinical finding/injury, 25.3% required the presence of multiple findings concurrently. Only 87 indications were evaluated in original research studies and only 9 by more than one study. CONCLUSION: The vast number, varying underlying content, and lack of original research relating to indications for DC suggests that substantial uncertainty exists around when the procedure is indicated and highlights the need to establish evidence-informed consensus indications.

Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis.

BACKGROUND: Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. QUESTIONS/PURPOSES: We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? METHODS: We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and metaregression. RESULTS: The pooled cumulative incidence of revision after hip or knee arthroplasty obtained using the Kaplan-Meier method was 1.55 times higher (95% confidence interval, 1.43-1.68; p < 0.001) than that obtained using the competing-risks method. Longer followup times and higher proportions of competing risks were not associated with increases in the amount of overestimation of revision risk by the Kaplan-Meier method (all p > 0.10). This may be due to the small number of studies that met the inclusion criteria and conservative variance approximation. CONCLUSIONS: The Kaplan-Meier method overestimates risk of revision after hip or knee arthroplasty in populations where competing risks (such as death) might preclude the occurrence of the event of interest (revision). Competing-risks methods should be used to more accurately estimate the cumulative incidence of revision when the goal is to plan healthcare services and resource allocation for revisions.

Clinical Presentation of Patients With Tension Pneumothorax: A Systematic Review.

OBJECTIVE: To determine whether the reported clinical presentation of tension pneumothorax differs between patients who are breathing unassisted versus receiving assisted ventilation. BACKGROUND: Animal studies suggest that the pathophysiology and physical signs of tension pneumothorax differ by subject ventilatory status. METHODS: We searched electronic databases through to October 15, 2013 for observational studies and case reports/series reporting clinical manifestations of tension pneumothorax. Two physicians independently extracted clinical manifestations reported at diagnosis. RESULTS: We identified 5 cohort studies (n = 310 patients) and 156 case series/reports of 183 cases of tension pneumothorax (n = 86 breathing unassisted, n = 97 receiving assisted ventilation). Hypoxia was reported among 43 (50.0%) cases of tension pneumothorax who were breathing unassisted versus 89 (91.8%) receiving assisted ventilation (P < 0.001). Pulmonary dysfunction progressed to respiratory arrest in 9.3% of cases breathing unassisted. As compared to cases who were breathing unassisted, the adjusted odds of hypotension and cardiac arrest were 12.6 (95% confidence interval, 5.8-27.5) and 17.7 (95% confidence interval, 4.0-78.4) times higher among cases receiving assisted ventilation. One cohort study reported that none of the patients with tension pneumothorax who were breathing unassisted versus 39.6% of those receiving assisted ventilation presented without an arterial pulse. In contrast to cases breathing unassisted, the majority (70.4%) of those receiving assisted ventilation who experienced hypotension or cardiac arrest developed these signs within minutes of clinical presentation. DISCUSSION: The reported clinical presentation of tension pneumothorax depends on the ventilatory status of the patient. This may have implications for improving the diagnosis and treatment of this life-threatening disorder.

Active Negative Pressure Peritoneal Therapy After Abbreviated Laparotomy: The Intraperitoneal Vacuum Randomized Controlled Trial.

OBJECTIVE: To determine whether active negative pressure peritoneal therapy with the ABThera temporary abdominal closure device reduces systemic inflammation after abbreviated laparotomy. BACKGROUND: Excessive systemic inflammation after abdominal injury or intra-abdominal sepsis is associated with poor outcomes. METHODS: We conducted a single-center, randomized controlled trial. Forty-five adults with abdominal injury (46.7%) or intra-abdominal sepsis (52.3%) were randomly allocated to the ABThera (n = 23) or Barker's vacuum pack (n = 22). On study days 1, 2, 3, 7, and 28, blood and peritoneal fluid were collected. The primary endpoint was the difference in the plasma concentration of interleukin-6 (IL-6) 24 and 48 hours after temporary abdominal closure application. RESULTS: There was a significantly lower peritoneal fluid drainage from the ABThera at 48 hours after randomization. Despite this, there was no difference in plasma concentration of IL-6 at baseline versus 24 (P = 0.52) or 48 hours (P = 0.82) between the groups. There was also no significant intergroup difference in the plasma concentrations of IL-1ß, -8, -10, or -12 p70 or tumor necrosis factor α between these time points. The cumulative incidence of primary fascial closure at 90 days was similar between groups (hazard ratio, 1.6; 95% confidence interval, 0.82-3.0; P = 0.17). However, 90-day mortality was improved in the ABThera group (hazard ratio, 0.32; 95% confidence interval, 0.11-0.93; P = 0.04). CONCLUSIONS: This trial observed a survival difference between patients randomized to the ABThera versus Barker's vacuum pack that did not seem to be mediated by an improvement in peritoneal fluid drainage, fascial closure rates, or markers of systemic inflammation. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01355094.

A protocol for a scoping and qualitative study to identify and evaluate indications for damage control surgery and damage control interventions in civilian trauma patients.

INTRODUCTION: Initial abbreviated surgery with planned reoperation (damage control surgery) is frequently used for major trauma patients to rapidly control haemorrhage while limiting surgical stress. Although damage control surgery may decrease mortality risk among the severely injured, it may also be associated with several complications when inappropriately applied. We seek to scope the literature on trauma damage control surgery, identify its proposed indications, map and clarify their definitions, and examine the content and evidence on which they are based. We also seek to generate a comprehensive list of unique indications to inform an appropriateness rating process. METHODS AND ANALYSIS: We will search 11 electronic bibliographic databases, included article bibliographies and grey literature sources for citations involving civilian trauma patients that proposed one or more indications for damage control surgery or a damage control intervention. Indications will be classified into a predefined conceptual framework and categorised and described using qualitative content analysis. Constant comparative methodology will be used to create, modify and test codes describing principal findings or injuries (eg, bilobar liver injury) and associated decision variables (eg, coagulopathy) that comprise the reported indications. After a unique list of codes have been developed, we will use the organisational system recommended by the RAND/University of California, Los Angeles (RAND-UCLA) Appropriateness Rating Method to group principal findings or injuries into chapters (subdivided by associated decision variables) according to broader clinical findings encountered during surgical practice (eg, major liver injury). ETHICS AND DISSEMINATION: This study will constitute the first step in a multistep research programme aimed at developing appropriate, evidence-informed indications for damage control in civilian trauma patients. With use of an integrated knowledge translation intervention that includes collaboration with surgical practice leaders, this research may allow for development of indications that are more likely to be relevant to and used by surgeons. Ethics approval is not required for this study.

Diagnostic accuracy of computed tomographic angiography for blunt cerebrovascular injury detection in trauma patients: a systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic accuracy of computed tomographic angiography (CTA) with digital subtraction angiography (DSA) for blunt cerebrovascular injury (BCVI) detection in trauma patients. BACKGROUND: Controversy exists as to whether the diagnostic performance of CTA compares favorably with the reference-standard, DSA. METHODS: We searched electronic databases (1950 to May 22, 2012), article bibliographies, conference proceedings (2008-2011), and clinical trial registries for studies comparing the accuracy of CTA with DSA for BCVI detection in trauma patients. Pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated using bivariate random effects models. RESULTS: Eight studies that examined 5704 carotid or vertebral arteries in 1426 trauma patients met inclusion criteria. The pooled sensitivity and specificity for BCVI detection with CTA versus DSA was 66% (95% CI, 49%-79%; I = 80.4%) and 97% (95% CI, 91%-99%; I = 94.6%), respectively. Corresponding pooled positive and negative likelihood ratios were 20.0 (95% CI, 6.9-58.4; I = 87.7%) and 0.35 (95% CI, 0.22-0.56; I = 74.9%), respectively. Although pooled sensitivity varied with the number of available CT slices, the training of interpreting radiologists, and in a pattern suggestive of differences in diagnostic threshold for judging CTA positivity, it remained 80% or less among studies that used scanners with 16 or more slices per rotation and where the CTA was read by neuroradiologists. CONCLUSIONS: Existing evidence suggests that the diagnostic performance of CTA varies considerably across studies, likely due to an implicit variation in diagnostic threshold across trauma centers. Moreover, although CTA appears to lack sensitivity to adequately rule out BCVI, it may be useful to rule in BCVI among trauma patients with a high pretest probability of injury.

Development of an online tool to determine appropriateness for an epilepsy surgery evaluation.

OBJECTIVES: Despite evidence that epilepsy surgery is more effective than medical therapy, significant delays between seizure intractability and surgery exist. We aimed to develop a new Web-based methodology to assist physicians in identifying patients who might benefit from an epilepsy surgery evaluation. METHODS: The RAND/UCLA appropriateness method was used. Clinical scenarios were developed based on eligibility criteria from previously published surgical series. Thirteen national experts rated the scenarios for their appropriateness for an epilepsy surgery evaluation based on published evidence. All scenarios were rerated after a face-to-face meeting following a modified Delphi process. Appropriate scenarios were rerated for necessity to determine referral priority. RESULTS: Of the final 2646 scenarios, 20.6% (n = 544) were appropriate, 17.2% (n = 456) uncertain, and 61.5% (n = 1626) inappropriate for a surgical evaluation. Of the appropriate cases, 55.9% (n = 306) were rated as very high priority. Not attempting AED treatment was always rated as inappropriate for a referral. Trial of 2 AEDs was usually rated as appropriate unless seizure-free or not fully investigated Based on these data, a Web-based decision tool (www.epilepsycases.com) was created. CONCLUSIONS: Using the available evidence through 2008 and expert consensus, we developed a Web-based decision tool that provides a guide for determining candidacy for epilepsy surgery evaluations. The tool needs clinical validation, and will be updated and revised regularly. This rendition of the tool is most appropriate for those over age 12 years with focal epilepsy. The Rand/UCLA appropriate methodology might be considered in the development of guidelines in other areas of epilepsy care.

Rationale for the prevention of syncope trial IV: assessment of midodrine.

BACKGROUND: Vasovagal syncope is a common problem associated with a poor quality of life, which improves when the frequency of syncope is reduced. Effective pharmacological therapies for vasovagal syncope have been elusive. Midodrine is a pro-drug whose primary metabolite is an alpha-1 adrenoreceptor agonist. A few studies have suggested that it may be beneficial in syncope, but all have had significant methodological limitations. A placebo-controlled clinical trial of midodrine for the prevention of vasovagal syncope is needed. STRUCTURE OF STUDY: The prevention of syncope trial IV (POST 4) is a multicenter, international, randomized, placebo-controlled study of midodrine in the prevention of vasovagal syncope. The primary end point is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive midodrine 10-30 mg/day or matching placebo, and followed for 1 year. Secondary end points include syncope frequency, presyncope, and quality of life. Primary analysis will be performed with an intention-to-treat approach, with a secondary on-treatment analysis. POWER CALCULATIONS: A total sample size of 112, split equally between the two groups, achieves 85 % power to detect a 50 % relative risk reduction when the event rates are 55 and 27.5 % in the placebo and midodrine arms. Allowing for 20 % dropout, we propose to enroll 140 patients. REGISTRATION: POST 4 is registered with http://www.clinicaltrials.gov (NCT01456481). IMPLICATIONS: This study will be the first adequately powered trial to determine whether midodrine is effective in preventing vasovagal syncope. If it is effective, then midodrine may become the first-line pharmacological therapy for this condition.

Functional outcomes for 2 years comparing hip resurfacing and total hip arthroplasty.

This prospective observational study of 499 patients with hip resurfacing and 255 patients with total hip arthroplasty compared outcomes for 2 years. We used propensity scores to identify matched cohorts of 118 patients with hip resurfacing and 118 patients with total hip arthroplasty. We used these cohorts to compare improvements in the Western Ontario and McMaster University (WOMAC) osteoarthritis index and Medical Outcomes Short-Form 36 physical function component (SF-36 PF) scores at 3 months and at 1 and 2 years postsurgery. Both groups demonstrated significant improvements from baseline in WOMAC and SF-36 PF. Improvements in SF-36 PF were greater for patients with hip resurfacing than for patients with total hip arthroplasty 1 and 2 years postsurgery; improvements in WOMAC were similar for both groups. The clinical significance of this observation needs further investigation.