Multicentre implementation of a quality improvement initiative to reduce delirium in adult intensive care units: An interrupted time series analysis.

PURPOSE: The ABCDEF bundle may improve delirium outcomes among intensive care unit (ICU) patients, however population-based studies are lacking. In this study we evaluated effects of a quality improvement initiative based on the ABCDEF bundle in adult ICUs in Alberta, Canada. MATERIAL AND METHODS: We conducted a pre-post, registry-based clinical trial, analysed using interrupted time series methodology. Outcomes were examined via segmented linear regression using mixed effects models. The main data source was a population-based electronic health record. RESULTS: 44,405 consecutive admissions (38,400 unique patients) admitted to 15 general medical/surgical and/or neurologic adult ICUs between 2014 and 2019 were included. The proportion of delirium days per ICU increased from 30.24% to 35.31% during the pre-intervention period. After intervention implementation it decreased significantly (bimonthly decrease of 0.34%, 95%CI 0.18-0.50%, p < 0.01) from 33.48% (95%CI 29.64-37.31%) in 2017 to 28.74% (95%CI 25.22-32.26%) in 2019. The proportion of sedation days using midazolam demonstrated an immediate decrease of 7.58% (95%CI 4.00-11.16%). There were no significant changes in duration of invasive ventilation, proportion of partial coma days, ICU mortality, or potential adverse events. CONCLUSIONS: An ABCDEF delirium initiative was implemented on a population-basis within adult ICUs and was successful at reducing the prevalence of delirium.

Impact of lifetime lactation on the risk and duration of frequent vasomotor symptoms: A longitudinal dose-response analysis.

OBJECTIVE: To examine the association between lifetime lactation and risk and duration of frequent vasomotor symptoms (VMS). DESIGN: Prospective cohort. SETTING: USA, 1995-2008. SAMPLE: 2356 parous midlife women in the Study of Women's Health Across the Nation. METHODS: Lifetime lactation was defined as the duration of breastfeeding across all births in months. We used generalised estimating equations to analyse risk of frequent VMS and Cox regression to analyse duration of frequent VMS in years. MAIN OUTCOME MEASURES: Frequent VMS (hot flashes and night sweats) were measured annually for 10 years, defined as occurring ≥6 days in the past 2 weeks. RESULTS: Overall, 57.1% of women reported hot flashes and 43.0% reported night sweats during follow-up. Lifetime lactation was inversely associated with hot flashes plateauing at 12 months of breastfeeding (6 months: adjusted odds ratio [AOR] 0.85, 95% confidence interval (CI) 0.75-0.96; 12 months: AOR 0.78, 95% CI 0.65-0.93) and was inversely associated with night sweats in a downward linear fashion (6 months: AOR 0.93, 95% CI 0.81-1.08; 18 months: AOR 0.82, 95% CI 0.67-1.02; 30 months: AOR 0.73, 95% CI 0.56-0.97). Lifetime lactation was associated with shorter duration of hot flashes and night sweats in a quadratic (bell-shaped) fashion. The association was strongest at 12-18 months of breastfeeding and significant for hot flashes (6 months: adjusted hazard ratio [AHR] 1.35, 95% CI 1.11-1.65; 18 months: AHR 1.54, 95% CI 1.16-2.03; 30 months: AHR 1.18, 95% CI 0.83-1.68). CONCLUSIONS: Longer lifetime lactation is associated with decreased risk and duration of frequent VMS.

Effect of Clinical Decision Support With Audit and Feedback on Prevention of Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Randomized Clinical Trial.

Importance: Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes. Objective: To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI. Design, Setting, and Participants: A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020. Interventions: During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention. Main Outcomes and Measures: The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models. Results: Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events. Conclusions and Relevance: Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT03453996.

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.

Pregnancy complications and risk of preterm birth according to maternal age: A population-based study of delivery hospitalizations in Alberta.

INTRODUCTION: Pregnancy-related medical complications are associated with a 2- to 5-fold increased risk of preterm birth (PTB), but the nature of this etiologic relation in context with maternal factors remains poorly understood. Previous studies have generally treated maternal age as a confounder but overlooked its potential as an effect modifier, whereby the magnitude of the effect of complications on PTB could differ significantly across age groups. We investigated whether advanced maternal age (≥35 years) modified the association between pregnancy complications and PTB, and compared population-attributable fractions of PTB from complications in women older vs younger than 35 years. MATERIAL AND METHODS: We analyzed population-based, cross-sectional data from the Alberta Discharge Abstract Database for women aged 18-50 years with singleton live births in hospital between 2014 and 2017 (n = 152 246). Complications were preeclampsia, gestational diabetes, and placental disorders identified using diagnostic codes. Outcomes were spontaneous (sPTB) or iatrogenic (iPTB) PTB before 37 weeks of gestation. We estimated risk ratios and risk differences using modified Poisson and log binomial regression, respectively, adjusting for confounders (pregnancy history, comorbidities). Population-attributable fractions estimates were calculated from risk ratios. Age modification was tested using interaction terms and Z-tests. RESULTS: Prevalence of advanced maternal age was 19.2%. Pregnancy complications and s/iPTB were more common among women aged ≥35 years. Age modified the risk of PTB from preeclampsia only, with risk differences of 9.9% (95% CI 7.2%-12.6%) in older women vs 6.1% (95% CI 4.8%-7.4%) in younger women (P-interaction = 0.012) for sPTB, and 29.5% (95% CI 26.0%-33.1%) vs 20.8% (95% CI 18.9%-22.6%, P-interaction <0.001) for iPTB. Population-attributable fractions of s/iPTB types for all complications were consistently 2%-5% larger in women aged ≥35 years, and significantly larger for preeclampsia (sPTB: 5.1% vs 2.7%, P = 0.002; iPTB: 18.8% vs 14.0%, P < 0.001) and placental disorders (sPTB: 12.5% vs 8.7%, P < 0.001; iPTB: 13.2% vs 8.9%, P < 0.001). CONCLUSIONS: Of the pregnancy complications studied, advanced maternal age only modified the association between PTB and preeclampsia, such that older women with preeclampsia have a higher risk for s/iPTB than younger counterparts. Pregnancy complications contribute to a sizable proportion of PTBs in Alberta, especially among women aged ≥35 years. Findings may inform clinical risk assessment and population-level policy targeting PTB.

Existing comorbidities in people with osteoarthritis: a retrospective analysis of a population-based cohort in Alberta, Canada.

OBJECTIVES: The purpose of this study is to estimate the prevalence of comorbidities among people with osteoarthritis (OA) using administrative health data. DESIGN: Retrospective cohort analysis. SETTING: All residents in the province of Alberta, Canada registered with the Alberta Health Care Insurance Plan population registry. PARTICIPANTS: 497 362 people with OA as defined by 'having at least one OA-related hospitalization, or at least two OA-related physician visits or two ambulatory care visits within two years'. PRIMARY OUTCOME MEASURES: We selected eight comorbidities based on literature review, clinical consultation and the availability of validated case definitions to estimate their frequencies at the time of diagnosis of OA. Sex-stratified age-standardised prevalence rates per 1000 population of eight clinically relevant comorbidities were calculated using direct standardisation with 95% CIs. We applied χ2 tests of independence with a Bonferroni correction to compare the percentage of comorbid conditions in each age group. RESULTS: 54.6% (n=2 71 794) of people meeting the OA case definition had at least one of the eight selected comorbidities. Females had a significantly higher rate of comorbidities compared with males (standardised rates ratio=1.26, 95% CI 1.25 to 1.28). Depression, chronic obstructive pulmonary disease (COPD) and hypertension were the most prevalent in both females and males after age-standardisation, with 40% of all cases having any combination of these comorbidities. We observed a significant difference in the percentage of comorbidities among age groups, illustrated by the youngest age group (<45 years) having the highest percentage of cases with depression (24.6%), compared with a frequency of 16.1% in those >65 years. CONCLUSIONS: Our findings highlight the high frequency of comorbidity in people with OA, with depression having the highest age-standardised prevalence rate. Comorbidities differentially affect females, and vary by age. These factors should inform healthcare programme and delivery.

Effect of Hearing Ability and Mild Behavioural Impairment on MoCA and Memory Index Scores.

BACKGROUND: The life-course model of modifiable risk factors for dementia now recognizes managing hearing loss and addressing social isolation. OBJECTIVE: To investigate the contribution and inter-relationship of hearing ability and behaviour change on cognitive ability. METHODS: We present the preliminary findings from a prospective longitudinal study of 35 non-demented participants ages 60-93, recruited from community rehabilitation and acute-care programs of Geriatric Medicine, who underwent baseline hearing, behavioural, and cognitive testing. RESULTS: After controlling for age and hearing impairment, the left ear Dichotic Digit Test (DDT) score accounted uniquely for 20% of the variance in MoCA Memory Index (p = .016 with ß = .598). Mild Behavioural Impairment (MBI) was highly prevalent, with 80% of older adults reporting at least one MBI symptom. People with hearing impairment had greater global MBI burden than people with normal hearing, especially in the domains of apathy and impulse dyscontrol; however, greater severity of hearing impairment was not associated with a higher number of neuropsychiatric symptoms (NPS). CONCLUSIONS: Low left DDT contributed to lower memory index and greater MBI burden is associated with hearing impairment. Our findings demonstrate the value of early non-invasive hearing and behavioural assessments as part of dementia risk assessment in older adults.

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.

Assessing the association between occupancy and outcome in critically Ill hospitalized patients with sepsis.

BACKGROUND: Sepsis has a high prevalence, mortality-rate and cost. Sepsis patients usually enter the hospital through the Emergency Department (ED). Process or structural issues related to care may affect outcome. METHODS: Multi-centered retrospective observational cohort study using administrative databases to identify adult patients (> = 18 years) with sepsis and severe sepsis admitted to Alberta Health Services Calgary zone adult multisystem intensive care units (ICU) through the ED between January 1, 2006 and September 30, 2009. We examined the association between ICU occupancy and hospital outcome. We explored other associations of hospital outcome including the effect of ED wait time, admission from ED during weekdays versus weekends and ED admission during the day versus at night. RESULTS: One thousand and seven hundred seventy patients were admitted to hospital via ED, 1036 (58.5 %) with sepsis and 734 (41.5 %) with severe sepsis. In patients with sepsis, ICU occupancy > 90 % was associated with an increase in hospital mortality even after adjusting for age, sex, triage level, Charlson index, time of first ED physician assessment and ICU admission. No differences in hospital mortality were found for patients who waited more than 7 h, were admitted during the day versus night or weekdays versus weekends. CONCLUSIONS: In patients with sepsis admitted via the ED, increased ICU occupancy was associated with higher in-hospital mortality.

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.