Methods for determination of optimal positive end-expiratory pressure: a protocol for a scoping review.

INTRODUCTION: Titrated application of positive end-expiratory pressure (PEEP) is an important part of any mechanical ventilation strategy. However, the method by which the optimal PEEP is determined and titrated varies widely. Methods for determining optimal PEEP have been assessed using a variety of different study designs and patient populations. We will conduct a scoping review to systematically identify all methods for determining optimal PEEP, and to identify the patient populations, outcomes measured and study designs used for each method. The goal will be to identify gaps in the optimal PEEP literature and identify areas where there may be an opportunity to further systematically synthesise and meta-analyse existing literature. METHODS AND ANALYSIS: Using scoping review methodology, we will generate a comprehensive search strategy based on inclusion and exclusion criteria generated using the population, concept, context framework. Five different databases will be searched (MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus). Three investigators will independently screen titles and abstracts, and two investigators will independently complete full-text review and data extraction. Included citations will be categorised in terms of PEEP method, study design, patient population and outcomes measured. The methods for PEEP titration will be described in detail, including strengths and limitations. ETHICS AND DISSEMINATION: Given this is a synthesis of existing literature, ethics approval is not required. The results will be disseminated to stakeholders via presentation at local, regional and national levels, as well as publication in a high-impact critical care journal. There is also the potential to impact local clinical care protocols and inform broader clinical practice guidelines undertaken by societies.

Risk Scores for Clinical Risk Stratification of Emergency Department Patients With Chest Pain but No Acute Myocardial Infarction: A Systematic Review.

BACKGROUND: Chest pain is a common cause for emergency department (ED) presentations. After myocardial infarction (MI) has been ruled out by means of electrocardiography and troponin testing, decisions around anatomic or functional testing may be informed by clinical risk scores. We conducted a systematic review to synthesize evidence of the prognostic performance of chest pain risk scores among ED patients who have had MI ruled out by means of a high-sensitivity troponin assay. METHODS: We queried multiple databases from inception to May 17, 2022. We included studies that quantified risk of 30-day major adverse cardiac events (MACE), at different cutoffs of clinical risk scores, among adult patients who had MI ruled out by means of a high-sensitivity troponin assay. Prognostic performance of each score was synthesized and described, but meta-analysis was not possible. RESULTS: Six studies met inclusion criteria. Short-term MACE risk among patients who had MI ruled out by means of high-sensitivity cardiac troponin assays was very low. The HEART score, with a cutoff of 3 or less, predicted a very low risk of MACE among the greatest proportion of patients. Other scores had lower sensitivity or classified fewer patients as low risk. CONCLUSIONS: The HEART score with a cutoff value of 3 or less accurately identified the greatest number of patients at low risk of 30-day MACE. However, MACE risk among patients who have MI ruled out by means of high-sensitivity troponin testing is sufficiently low that clinical risk stratification or noninvasive testing may be of little additional value in identifying patients with coronary disease.

Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis.

BACKGROUND: Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. METHODS: Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. RESULTS: Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8-46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. CONCLUSIONS: Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.

Rehabilitation therapies in Rett syndrome across the lifespan: A scoping review of human and animal studies.

PURPOSE: To perform a scoping review of the evidence for therapeutic interventions to manage functional impairments associated with Rett syndrome (RTT) throughout the lifespan. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL, CINAHL, Scopus and Index to Chiropractic Literature were searched systematically up to December 2019. Two investigators independently reviewed all search results and extracted those that met the inclusion criteria. Human and animal model studies pertaining to therapies that increase functional ability or treat RTT-associated symptoms in all age groups were included. Relevant studies were grouped into intervention categories and rated using the Oxford Centre of Evidence Based Medicine Levels of Evidence. Demographics of participants, interventions, and outcomes were summarized. RESULTS: Ninety-one articles representing 88 studies met the inclusion criteria, of which 80 were human clinical studies and eight were studies using animal models. Study designs were primarily case series and only six studies involved participants above the age of 40. CONCLUSION: A small number of rigorously studied rehabilitation interventions have been published. Published studies aim to address a wide variety of functional impairments. Research regarding implementation of therapies for older patients with RTT is lacking and requires further exploration.

Evaluation of interventions to improve electronic health record documentation within the inpatient setting: a protocol for a systematic review.

BACKGROUND: Electronic health records (EHRs) are increasing in popularity across national and international healthcare systems. Despite their augmented availability and use, the quality of electronic health records is problematic. There are various reasons for poor documentation quality within the EHR, and efforts have been made to address these areas. Previous systematic reviews have assessed intervention effectiveness within the outpatient setting or within paper documentation. This systematic review aims to assess the effectiveness of different interventions seeking to improve EHR documentation within an inpatient setting. METHODS: We will employ a comprehensive search strategy that encompasses four distinct themes: EHR, documentation, interventions, and study design. Four databases (MEDLINE, EMBASE, CENTRAL, and CINAHL) will be searched along with an in-depth examination of the grey literature and reference lists of relevant articles. A customized hybrid study quality assessment tool has been designed, integrating components of the Downs and Black and Newcastle-Ottawa Scales, into a REDCap data capture form to facilitate data extraction and analysis. Given the predicted high heterogeneity between studies, it may not be possible to standardize data for a quantitative comparison and meta-analysis. Thus, data will be synthesized in a narrative, semi-quantitative manner. DISCUSSION: This review will summarize the current level of evidence on the effectiveness of interventions implemented to improve inpatient EHR documentation, which could ultimately enhance data quality in administrative health databases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017083494.

Effect of maternal mental health improvement programs on obesity in pediatric populations: a protocol for a systematic review and meta-analysis.

BACKGROUND: Childhood obesity has become a global epidemic irrespective of the socioeconomic status of a country or nation. Obesity increases the risk of various diseases in children, for example asthma, sleep apnea, bone and joint problems, type-2 diabetes, and heart problems. The existing literature informs us of the many factors associated with childhood obesity. Among these factors, maternal mental health has been found to be a strong predictor. Maternal mental health programs were implemented to address the issue of childhood obesity but with little or no improvement. It suggests systematically reviewing the literature to assess the contents of these programs and carrying out meta-analysis for the overall effect of these interventions. METHODS: The studies included in this review will be experimental designs such as randomized controlled trials (RCTs) which provide information on interventions to improve maternal mental health and its effects on childhood obesity. We plan to search MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, ERIC, CINAHL, ProQuest Dissertations and Theses Global, Scopus, and Web of Science with no restrictions as to language. Reference lists of the selected articles will also be searched for additional articles. The Cochrane EPOC Risk of Bias Tool will be used to assess the quality of studies. If the studies lend themselves to a statistical analysis, we will also carry out a meta-analysis. DISCUSSION: This review will help determine the effect of maternal health improvement programs on childhood obesity. These findings, in turn, will guide the research community on the development of related programs in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42017072737 .

The Accuracy and Prognostic Value of Point-of-care Ultrasound for Nephrolithiasis in the Emergency Department: A Systematic Review and Meta-analysis.

INTRODUCTION: Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis and 2) to assess its prognostic value in the management of renal colic. METHODS: The review protocol was registered to the PROSPERO database (CRD42016035331). An electronic database search of MEDLINE, Embase, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were computed tomography evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by consensus with a third reviewer. Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary objective of prognostic value was reported as a narrative summary. RESULTS: The electronic search yielded 627 unique titles. After relevance screening, 26 papers underwent full-text review, and nine articles met all inclusion criteria. Of these, five high-quality studies (N = 1,773) were included in the meta-analysis for diagnostic accuracy and the remaining yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% confidence interval [CI] = 67.1%-73.2%) and 75.4% (95% CI = 72.5%-78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect. Two of the studies in the meta-analysis found that the finding of moderate or greater hydronephrosis yielded a specificity of 94.4% (95% CI = 92.7%-95.8%). Four studies examining prognostic value noted a higher likelihood of a large stone when positive POCUS findings were present. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation. CONCLUSION: Point-of-care ultrasound has modest diagnostic accuracy for diagnosing nephrolithiasis. The finding of moderate or severe hydronephrosis is highly specific for the presence of any stone, and the presence of any hydronephrosis is suggestive of a larger (>5 mm) stone in those presenting with renal colic.

The effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women: a protocol for systematic review and meta-analysis.

BACKGROUND: The prevalence of menopause in women with or at risk of chronic kidney disease is increasing globally. Although international guidelines on menopause recommend the use of postmenopausal hormone therapy with or without selective estrogen receptor modulators for control of vasomotor symptoms, the effects of these treatments on kidney function and albuminuria are unclear. Furthermore, women with chronic kidney disease are at significantly increased risk of venous thromboembolism and malignancy, well-documented adverse effects of postmenopausal hormone therapy. Our study aims to establish the effect of these treatments on kidney function and albuminuria in women, as well as determine the safety of these treatments in the chronic kidney disease population. METHODS: We will conduct a systematic review and meta-analysis addressing the effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women. We plan to search for published (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), tables of contents of relevant journals) and unpublished (ongoing studies, conference proceedings) studies in all languages examining the effect of postmenopausal hormone therapy, including selective estrogen receptor modulators, on kidney function and albuminuria, as well as the risk of adverse outcomes of these treatments in women with chronic kidney disease. Two independent investigators will screen identified abstracts and select studies that examine the effect of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in the general population or adverse outcomes in the chronic kidney disease population. Data on study population, intervention, outcomes, as well as study quality and risk of bias will be independently extracted from each eligible study. Along with descriptive presentation of data, outcome measures will be presented as meta-analyses using a random effects model. Planned subgroup analyses will be completed, and meta-regression will be performed if significant heterogeneity is noted. DISCUSSION: By examining the effects of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney function and albuminuria, the results of this systematic review and meta-analysis will inform management of postmenopausal women in the general population. Furthermore, it will evaluate the safety, including the risks of known adverse outcomes of postmenopausal hormone therapy and selective estrogen receptor modulators, in the already vulnerable chronic kidney disease population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016050651.

Intratracheal Administration of Budesonide-Surfactant in Prevention of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis.

Despite the near universal adaptation of gentle mechanical ventilation, surfactant use and non-invasive respiratory support, bronchopulmonary dysplasia (BPD) remains one of the most common respiratory morbidities in very low birth weight (VLBW) infants. Thus, the objective of this review was to evaluate the efficacy of intra-tracheal administration of budesonide-surfactant mixture in preventing bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants. MEDLINE, EMBASE, and PubMed were searched for randomized clinical trials in which intra-tracheal administration of budesonide-surfactant was used to prevent BPD in infants. The primary outcomes were BPD and composite outcome of death or BPD. Meta-analysis of the two clinical trials revealed that infants who received intra-tracheal instillation of budesonide-surfactant mixture demonstrated 43% reduction in the risk of BPD (RR: 0.57; 95%CI: 0.43-0.76, NNT = 5). Although mortality was not different between the groups (OR: 0.61; 95%CI: 0.34-1.04), a 40% reduction was observed in the composite outcome of death or BPD in the budesonide-surfactant group (RR: 0.60; 95%CI: 0.49-0.74, NNT = 3). Thus, this review concludes that intra-tracheal administration of budesonide-surfactant combination was associated with decreased incidence of BPD alone or composite outcome of death or BPD in VLBW infants though there is a need for larger trials before it can be recommended as a standard of care.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

A Systematic Review of Psychiatric, Psychological, and Behavioural Outcomes following Mild Traumatic Brain Injury in Children and Adolescents.

BACKGROUND: Evidence regarding longer-term psychiatric, psychological, and behavioural outcomes (for example, anxiety, mood disorders, depression, and attention disorders) following mild traumatic brain injury (mTBI) in children and adolescents has not been previously synthesized. OBJECTIVE: To conduct a systematic review of the available evidence examining psychiatric, psychological, and behavioural outcomes following mTBI in children and adolescents. MATERIALS AND METHODS: Nine electronic databases were systematically searched from 1980 to August 2014. Studies selected met the following criteria: original data; study design was a randomized controlled trial, quasi-experimental design, cohort or historical cohort study, case-control study, or cross-sectional study; exposure included mTBI (including concussion); population included children and adolescents (<19 years) at the time of mTBI, as well as a comparison group (for example, healthy children, children with orthopaedic injuries); and included psychiatric, psychological, or behavioural outcomes (for example, anxiety, mood disorders, depression, attention disorders). Two authors independently assessed the quality and level of evidence with the Downs and Black (DB) criteria and Oxford Centre of Evidence-Based Medicine (OCEBM) model, respectively, for each manuscript. RESULTS: Of 9472 studies identified in the initial search, 30 were included and scored. Heterogeneity in methodology and injury definition precluded meta-analyses. The median methodological quality for all 30 studies, based on the DB criteria, was 15/33 (range 6 to 19). The highest level of evidence demonstrated by all reviewed studies was level 2b based on OCEBM criteria, with the majority (28/30 studies) classified at this level. Based on the literature included in this systematic review, psychological and psychiatric problems in children with a history of mTBI were found to be more prevalent when mTBI is associated with hospitalization, when assessment occurs earlier in the recovery period (that is, resolves over time), when there are multiple previous mTBIs, in individuals with preexisting psychiatric illness, when outcomes are based on retrospective recall, and when the comparison group is noninjured healthy children (as opposed to children with injuries not involving the head). CONCLUSIONS: Overall, few rigorous prospective studies have examined psychological, behavioural, and psychiatric outcomes following mTBI. In the absence of true reports of preinjury problems and when ideally comparing mild TBI to non-TBI injured controls, there is little evidence to suggest that psychological, behavioural, and/or psychiatric problems persist beyond the acute and subacute period following an mTBI in children and adolescents.

Inflammatory mediators in intra-abdominal sepsis or injury - a scoping review.

INTRODUCTION: Inflammatory and protein mediators (cytokine, chemokine, acute phase proteins) play an important, but still not completely understood, role in the morbidity and mortality of intra-abdominal sepsis/injury. We therefore systematically reviewed preclinical and clinical studies of mediators in intra-abdominal sepsis/injury in order to evaluate their ability to: (1) function as diagnostic/prognostic biomarkers; (2) serve as therapeutic targets; and (3) illuminate the pathogenesis mechanisms of sepsis or injury-related organ dysfunction. METHODS: We searched MEDLINE, PubMed, EMBASE and the Cochrane Library. Two investigators independently reviewed all identified abstracts and selected articles for full-text review. We included original studies assessing mediators in intra-abdominal sepsis/injury. RESULTS: Among 2437 citations, we selected 182 studies in the scoping review, including 79 preclinical and 103 clinical studies. Serum procalcitonin and C-reactive protein appear to be useful to rule out infection or monitor therapy; however, the diagnostic and prognostic value of mediators for complications/outcomes of sepsis or injury remains to be established. Peritoneal mediator levels are substantially higher than systemic levels after intra-abdominal infection/trauma. Common limitations of current studies included small sample sizes and lack of uniformity in study design and outcome measures. To date, targeted therapies against mediators remain experimental. CONCLUSIONS: Whereas preclinical data suggests mediators play a critical role in intra-abdominal sepsis or injury, there is no consensus on the clinical use of mediators in diagnosing or managing intra-abdominal sepsis or injury. Measurement of peritoneal mediators should be further investigated as a more sensitive determinant of intra-abdominal inflammatory response. High-quality clinical trials are needed to better understand the role of inflammatory mediators.

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.

Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review.

BACKGROUND: Hypoxic-ischemic injury is thought to play a significant role in necrotizing enterocolitis (NEC). Nitric Oxide (NO) is the principal inhibitory neurotransmitter in the gut and is involved in regulation of mucosal blood flow and maintenance of mucosal integrity. NO is synthesized from L-arginine by NO synthases. Our primary objective was to determine the effectiveness of supplemental L-arginine versus placebo in prevention of NEC in preterm infants ≤ 34 weeks gestational age by systematic review of published randomized controlled trials (RCTs). METHODS: This review included RCTs in which L-arginine was administered as a supplement to neonates to prevent NEC. Searches were conducted in OVID MEDLINE, EMBASE, PubMed, and CINAHL from their dates of inception to July, 2014. Inclusion criteria were informed parental consent, neonates born at ≤ 34 weeks gestation, and birth weight ≤ 1500 g. Exclusion criteria included neonates with severe congenital anomalies and inborn errors of metabolism. Incidence of NEC was the primary outcome measure. Whole data were analyzed by RevMan 5.1 (Update Software, Oxford, UK). Outcome data were analyzed to determine risk ratios, number needed to treat, confidence intervals, and test for overall effect. RESULTS: Two trials including 425 neonates were eligible for this review. Of these, 235 neonates were included in the study. L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02). A similar finding was identified for all stages of NEC (60% reduction, RR 0.40, 95% CI 0.23 to 0.69, NNT = 5) (P = 0.001). At age 3 yrs, there was no significant difference between the 2 groups in terms of any neurodevelopmental disability (RR 0.65; 95% CI 0.23-1.83, P = 0.41). CONCLUSIONS: L-arginine supplementation appears to be protective in prevention of NEC in preterm infants and without any significant impact on neurodevelopmental outcomes at 36 months of corrected age. With the addition of the results of one more study to the literature, an intriguing role for L-arginine supplementation continues to gain support. However, large multi-centre RCTs are needed before this can become common practice.

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.

Clinical manifestations of tension pneumothorax: protocol for a systematic review and meta-analysis.

BACKGROUND: Although health care providers utilize classically described signs and symptoms to diagnose tension pneumothorax, available literature sources differ in their descriptions of its clinical manifestations. Moreover, while the clinical manifestations of tension pneumothorax have been suggested to differ among subjects of varying respiratory status, it remains unknown if these differences are supported by clinical evidence. Thus, the primary objective of this study is to systematically describe and contrast the clinical manifestations of tension pneumothorax among patients receiving positive pressure ventilation versus those who are breathing unassisted. METHODS/DESIGN: We will search electronic bibliographic databases (MEDLINE, PubMed, EMBASE, and the Cochrane Database of Systematic Reviews) and clinical trial registries from their first available date as well as personal files, identified review articles, and included article bibliographies. Two investigators will independently screen identified article titles and abstracts and select observational (cohort, case-control, and cross-sectional) studies and case reports and series that report original data on clinical manifestations of tension pneumothorax. These investigators will also independently assess risk of bias and extract data. Identified data on the clinical manifestations of tension pneumothorax will be stratified according to whether adult or pediatric study patients were receiving positive pressure ventilation or were breathing unassisted, as well as whether the two investigators independently agreed that the clinical condition of the study patient(s) aligned with a previously published tension pneumothorax working definition. These data will then be summarized using a formal narrative synthesis alongside a meta-analysis of observational studies and then case reports and series where possible. Pooled or combined estimates of the occurrence rate of clinical manifestations will be calculated using random effects models (for observational studies) and generalized estimating equations adjusted for reported potential confounding factors (for case reports and series). DISCUSSION: This study will compile the world literature on tension pneumothorax and provide the first systematic description of the clinical manifestations of the disorder according to presenting patient respiratory status. It will also demonstrate a series of methods that may be used to address difficulties likely to be encountered during the conduct of a meta-analysis of data contained in published case reports and series. PROSPERO registration number: CRD42013005826.

Incidence, prevalence, and occurrence rate of infection among adults hospitalized after traumatic brain injury: study protocol for a systematic review and meta-analysis.

BACKGROUND: Infection occurs commonly among patients hospitalized after traumatic brain injury (TBI) and has been associated with increased intensive care unit and hospital lengths of stay and an elevated risk of poor neurological outcome and mortality. However, as many relevant published studies to date have varied in the type and severity of TBI among included patients as well as in their design (randomized versus non-randomized), risk of bias, and setting (hospital ward versus intensive care unit), their reported estimates of infection occurrence vary considerably. Thus, the purpose of this systematic review and meta-analysis is to estimate the incidence, prevalence, and occurrence rate of infection among patients hospitalized after TBI. METHODS/DESIGN: We will search electronic bibliographic databases (MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews) from their first available date as well as personal files, reference lists of included articles, and conference proceedings. Two investigators will independently screen titles and abstracts and select cohort studies, cross-sectional studies, and randomized controlled trials involving adults hospitalized after TBI that reported estimates of cumulative incidence, incidence rate, prevalence, or occurrence rate of infection for inclusion in the systematic review. These investigators will also independently extract data and assess risk of bias. We will exclude studies with fewer than ten patients; experimental groups allocated to treatment with antibiotics, glucocorticoids, immunosuppressants, barbiturates, or hypothermia; and studies focused on military/combat-related TBI. Pooled estimates of cumulative incidence, incidence rate, prevalence, and occurrence rate will be calculated using random effects models. We will also calculate I2 and Cochran Q statistics to assess for inter-study heterogeneity and conduct stratified analyses and univariate meta-regression to determine the influence of pre-defined study-level covariates on our pooled estimates. DISCUSSION: This study will compile the world literature regarding the epidemiology of infection among adults hospitalized after TBI. A better understanding of the role of infection will be helpful in the development of guidelines for patient management. This protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42013005146).

Negative-pressure wound therapy for critically ill adults with open abdominal wounds: a systematic review.

BACKGROUND: Open abdominal management with negative-pressure wound therapy (NPWT) is increasingly used for critically ill trauma and surgery patients. We sought to determine the comparative efficacy and safety of NPWT versus alternate temporary abdominal closure (TAC) techniques in critically ill adults with open abdominal wounds. METHODS: We conducted a systematic review of published and unpublished comparative studies. We searched MEDLINE, PubMed, EMBASE, Scopus, Web of Science, the Cochrane Database, the Center for Reviews and Dissemination, clinical trials registries, and bibliographies of included articles. Two authors independently abstracted data on study design, methodological quality, patient characteristics, and outcomes. RESULTS: Among 2,715 citations identified, 2 randomized controlled trials and 9 cohort studies (3 prospective/6 retrospective) met inclusion criteria. Methodological quality of included prospective studies was moderate. One randomized controlled trial observed an improved fascial closure rate (relative risk [RR], 2.4; 95% confidence interval [CI], 1.0-5.3) and length of hospital stay after addition of retention sutured sequential fascial closure to the Kinetic Concepts Inc. (KCI) vacuum-assisted closure (VAC). Another reported a trend toward enhanced fascial closure using the KCI VAC versus Barker's vacuum pack (RR, 2.6; 95% CI, 0.95-7.1). A prospective cohort study observed improved mortality (RR, 0.48; 95% CI, 0.25-0.92) and fascial closure (RR, 1.5; 95% CI, 1.1-2.0) for patients who received the ABThera versus Barker's vacuum pack. Another noted a reduced arterial lactate, intra-abdominal pressure, and hospital stay for those fitted with the KCI VAC versus Bogotá bag. Most included retrospective studies exhibited low methodological quality and reported no mortality or fascial closure benefit for NPWT. CONCLUSION: Limited prospective comparative data suggests that NPWT versus alternate TAC techniques may be linked with improved outcomes. However, the clinical heterogeneity and quality of available studies preclude definitive conclusions regarding the preferential use of NPWT over alternate TAC techniques. LEVEL OF EVIDENCE: Systematic review, level III.

Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials.

OBJECTIVES: To summarize randomized controlled trials on the effects of sedative agents on neurologic outcome, mortality, intracranial pressure, cerebral perfusion pressure, and adverse drug events in critically ill adults with severe traumatic brain injury. DATA SOURCES: PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles. STUDY SELECTION: Randomized controlled trials of propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, α-2 agonist, and antipsychotic drug classes for management of adult intensive care unit patients with severe traumatic brain injury. DATA EXTRACTION: In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results. DATA SYNTHESIS: Among 1,892 citations, 13 randomized controlled trials enrolling 380 patients met inclusion criteria. Long-term sedation (≥24 hrs) was addressed in six studies, whereas a bolus dose, short infusion, or doubling of plasma drug concentration was investigated in remaining trials. Most trials did not describe baseline traumatic brain injury prognostic factors or important cointerventions. Eight trials possibly or definitely concealed allocation and six were blinded. Insufficient data exist regarding the effects of sedative agents on neurologic outcome or mortality. Although their effects are likely transient, bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure. In one study, a long-term infusion of propofol vs. morphine was associated with a reduced requirement for intracranial pressure-lowering cointerventions and a lower intracranial pressure on the third day. Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure. CONCLUSIONS: This systematic review found no convincing evidence that one sedative agent is more efficacious than another for improvement of patient-centered outcomes, intracranial pressure, or cerebral perfusion pressure in critically ill adults with severe traumatic brain injury. High bolus doses of opioids, however, have potentially deleterious effects on intracranial pressure and cerebral perfusion pressure. Adequately powered, high-quality, randomized controlled trials are urgently warranted.