Potential Mortality Benefit Research Articles

Racial Differences in Adherence to Lung Cancer Screening Follow-up: A Systematic Review and Meta-analysis

In 2013, the United States Preventive Services Taskforce instituted recommendations for annual lung cancer screening (LCS) with low-dose chest CT imaging for high-risk individuals. LCS reduces lung cancer mortality, with greater reduction observed in Black participants in clinical trials. Although racial disparities in lung cancer mortality have been well documented, less is known about disparities in LCS participation and adherence to follow-up in clinical practice.What is the association between race and adherence to LCS follow-up?A systematic review was conducted through a search of published studies in MEDLINE, PubMed, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health Literature Database from database inception through October 2020. We included studies that examined rates of adherence to LCS follow-up and compared rates by race. Studies were pooled using random-effects meta-analysis.We screened 18,300 titles and abstracts, and 229 studies were selected for full-text review. Nine studies met inclusion criteria; seven were included in the meta-analysis. Median adherent follow-up rate was 37% (range, 16%-82%). Notable differences among the studies included the proportion of the Black population (range, 4%-47%) and the structure of the LCS programs. The meta-analyses showed lower adherence to LCS follow-up in the Black population (OR, 0.67; 95% CI, 0.55-0.80). This disparity persisted across all malignancy risk levels determined by initial screening results.Lower adherence to LCS follow-up in Black compared with White patients occurs despite the higher potential lung cancer mortality benefit. Literature specifically addressing race-related barriers to LCS adherence remains limited. To ensure equity in LCS benefits, greater outreach to eligible Black patients should be implemented through increased physician education and use of screening program coordinators to focus on this patient population.PROSPERO; No.: CRD42020214213; URL: http://www.crd.york.ac.uk/PROSPERO.

Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive Pulmonary Disease.

To review current evidence on the use of a fixed-dose combination (FDC) of budesonide/glycopyrrolate/formoterol fumarate (BGFF) triple therapy delivered via metered dose inhaler (MDI) in patients with chronic obstructive pulmonary disease (COPD) and offer clinical practice insights. We used PubMed to conduct the literature search from 1946 through June 30, 2021, using budesonide, glycopyrrolate or glycopyrronium, and formoterol. We included clinical trials in patients with COPD along with pharmacokinetic or pharmacodynamic studies. In all, 19 citations were included. BGFF MDI reduces the risk of exacerbations regardless of exacerbation history compared with dual bronchodilators or inhaled corticosteroid/long-acting β-agonist. Rescue inhaler use decreased, and patient-reported outcomes of symptoms and well-being improved with triple therapy. Mortality was decreased with the higher-dose BGFF MDI in comparison to dual bronchodilator therapy. Dysphonia and candidiasis were more common with BGFF MDI compared with dual bronchodilators, as was pneumonia. BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia. The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.

Accelerating the Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: A Risk of Combining Dexamethasone and Tocilizumab for Severe Coronavirus Disease 2019.

Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the interleukin 6 receptor antagonist tocilizumab in severe coronavirus disease 2019. Conversely, dual immunomodulation may weaken antiviral responses and delay viral clearance, allowing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to expand its population and accrue genetic diversity within individual hosts. Generating a pool of hosts with genetically diverse viral populations while introducing new selective pressures in the form of vaccination-induced immunity could accelerate the process of antigenic drift in SARS-CoV-2. However, clinical trials to date have largely disregarded viral outcomes, and data on viral kinetics in response to immunomodulation are scarce. Coadministration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.

Early National Landscape of Surgical Stabilization of Sternal Fractures.

Operative management of chest wall injuries aims to restore respiratory mechanics and mitigate pulmonary complications. Extensive studies support surgical stabilization of rib fractures (SSRF) for select patients, but role for surgical stabilization of sternal fractures (SSSF) remains unclear. We aimed to understand national prevalence of SSSF and compare outcomes after surgical stabilization and non-operative management of sternal fractures. We retrospectively analyzed adult patients (age ≥ 18years) admitted with sternal fractures after blunt trauma using the 2016 National Trauma Data Bank. We compared odds of inpatient mortality, pneumonia, and respiratory failure for propensity score matched patients (4:1) who underwent non-operative management vs SSSF. We characterized subgroup of patients with concurrent rib and sternal fractures who underwent concomitant SSRF-SSSF. We identified 14,760 encounters of adults admitted with sternal fractures; 270 (1.8%) underwent SSSF. Compared to matched patients who underwent non-operative management, patients who underwent SSSF had lower odds of mortality (OR [95%CI]: 0.19 [0.06-0.62], p = 0.006). Adjusted for trauma center level, Mantel-Haenszel mortality odds remained lower for patients who underwent SSSF. Odds of pneumonia and respiratory failure were similar between matched groups. Among 46% of patients who had concomitant rib fractures, 0.3% (n = 18) underwent concurrent SSRF-SSSF and these patients survived hospitalization without pneumonia or respiratory failure. A vast majority of patients who suffer sternal fractures undergo non-operative management. Potential mortality benefit of SSSF and concurrent SSRF-SSSF's role for commonly concomitant rib and sternal fractures deserve further study. Our preliminary findings call for delineating heterogeneity of sternal fractures and establishing consensus SSSF indications.

A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy.

IntroductionFluid therapy in critically ill patients, especially timing and fluid choice, is controversial. Previous randomized trials produced conflicting results. This observational study evaluated the effect of colloid use on 90-day mortality and acute kidney injury (RIFLE F) within the Rational Fluid Therapy in Asia (RaFTA) registry in intensive care units.Materials and methodsRaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI).ResultsTwenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635).ConclusionRaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition.Clinical significanceEarly resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research.How to cite this articleJacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028–1036.

Endovascular treatment of peripheral artery disease is associated with improved central hemodynamics and ventricular function

Abstract Background Peripheral artery disease (PAD) is a major manifestation of atherosclerosis and a risk factor for morbidity and mortality. PAD itself is associated with increased arterial stiffness with impact on cardiac functions. Previous studies have demonstrated that augmentation index (AIx) and central blood pressure (CBP) correlate with increased cardiovascular mortality. This mechanism has been described as arterio-ventricular (AV) coupling with altered ventricular afterload and a depressed ventricular function, measured by global longitudinal strain (GLS). The impact of PAD-related endovascular treatment on arterial stiffness, central hemodynamics and potential impact on AV coupling has not been elucidated until now. Purpose Aim of the study was to investigate, if endovascular treatment of PAD improves cardiac function via enhanced central hemodynamics and AV coupling. Methods To this aim 77 patients with known symptomatic PAD who underwent interventions in the iliac and femoropopliteal arteries were included in a cross-sectional study. AIx, CBP and GLS were determined using dedicated waveform analysis and echocardiography before and after endovascular treatment. Results Mean age was 65.1±10.4 years with 66.2% male patients. Symptoms were classified by Fontaine classification (stage IIb 80.7%, stage III 5.8% and stage IV 13.5%). Iliac vessel intervention was performed in 16 and femoropopliteal intervention in 61 cases. A stentless approach was feasible in 55 patients with DCB treatment and atherectomy. After endovascular treatment, peripheral perfusion was enhanced (ABI 0.45±0.6 vs 0.81±0.5, p&amp;lt;0.0001). Moreover, central hemodynamics were improved (AIX 33.7±3% vs 27.9±2%, p=0.0008; AP 17.8±2 mmHg vs 14.0±2 mmHg, p=0.0004; central PP 52.4±6 mmHg vs 46.4±6 mmHg, p=0.0001). Impressively, left ventricular function was also significantly improved (GLS −15.7±2.3% vs −17.1±2.8%, p=0.005) with an improvement in AV coupling (PWV/GLS ratio −0.58m/sec% vs −0.56m/sec%, p&amp;lt;0.01). Conclusion Our results demonstrate that endovascular treatment of the peripheral vessels is associated with an improvement of central hemodynamics and left ventricular function via enhanced AV coupling. These prognostic relevant markers of cardiovascular disease could point to an overall potential mortality benefit through PAD treatment. Further investigation of the underlying mechanisms of AV coupling in the setting of endovascular treatment of PAD with impact on cardiovascular mortality is needed in this high-risk population. Funding Acknowledgement Type of funding source: None

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

Potential unrealized mortality benefit of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transport-2 inhibitors: A report from the Veterans Health Administration Clinical Assessment, Reporting and Tracking program.

To assess the unrealized potential of glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose co-transport-2 inhibitor (SGLT2i) use to reduce mortality in veterans with type 2 diabetes (T2D), coronary artery disease (CAD), and other characteristics congruent with clinical trial cohorts that established the efficacy of these agents. Veterans with T2D and CAD on angiography in 2014 who were untreated with either a GLP-1RA or a SGLT2i were assessed for key eligibility criteria of the LEADER (GLP-1RA) and EMPA-REG OUTCOME (SGLT2i) trials. Trial hazard ratios and 95% confidence intervals for all-cause death were applied to deaths observed in veterans through 2018 to estimate the potential benefit of GLP-1RA or SGLT2i use. Median observation was 4.3 years. Of 15 987 veterans with T2D and CAD, 1186 (7.4%) were excluded for GLP-1RA or SGLT2i treatment, and 1386 lacked glycated haemoglobin measurement. Of the remaining 13 415 patients, 4103 (30.1%) and 5313 (39.6%) fulfilled the key criteria for the LEADER and EMPA-REG OUTCOME trials, respectively. Death occurred in 1009 (24.6%) of LEADER-eligible patients and 1335 (25.1%) of EMPA-REG OUTCOME-eligible patients. Under treatment with liraglutide in LEADER-eligible veterans, a 3.5% (0.7%-6.2%) potential absolute mortality reduction, corresponding to 144 (28-253) fewer deaths (0.88 [0.17-1.56] per 100 person-years), might have been expected. Similarly, under treatment with empagliflozin in EMPA-REG OUTCOME-eligible veterans, a 7.9% (4.5%-10.8%) potential absolute mortality reduction, corresponding to 418 (230-573) fewer deaths (1.98 [1.14-2.72] per 100 person-years), might have been expected. This analysis indicates unrealized opportunities to reduce mortality in selected veterans with T2D and CAD via increased GLP-1RA and SGLT2i use.

Charlson Comorbidity Index Is a Useful Predictor of Patients Death Prior to Interval Colonoscopy (Poster Presentation)

Societal recommendations rely on age and life expectancy to guide clinicians on the potential mortality benefit of continued colorectal cancer (CRC) screening. Up to 40% of patients undergoing screening colonoscopy have less than a 10-year life expectancy, highlighting this clinical challenge. The Charlson Comorbidity Index (CCI) has been utilized to prognosticate mortality for a number of conditions but has not been examined for use in screening colonoscopy recommendations. We sought to examine whether CCI could be used to predict patient death (i.e., patients who should discontinue colonoscopy) prior to the recommended screening or surveillance procedure.

Potential Treatments for SARS-CoV-2 Infection.

Potential Treatments for SARS-CoV-2 Infection.

Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial

Sepsis is a major public health burden resulting in 25%to 30%in-hospital mortality and accounting for over 20 billion dollars of US hospital costs. Does hydrocortisone, ascorbic acid, thiamine (HAT) therapy improve clinical outcomes in sepsis and septic shock? This was a randomized, double-blinded, placebo-controlled trial conducted from February 2018 to June 2019, assessing an HAT treatment bundle for the management of septic and septic shock patients admitted to an ICU. The primary outcomes were resolution of shock and change in Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes included 28-day mortality, ICU mortality, hospital mortality, procalcitonin clearance (PCT-c), hospital length of stay (LOS), ICU LOS, and ventilator-free days. One hundred thirty-seven patients were randomized to the treatment group (n= 68) and comparator group (n= 69), respectively, with no significant differences in baseline characteristics. A statistically significant difference was found in the time patients required vasopressors, indicating quicker reversal of shock in the HAT group compared with the comparator group (27 ± 22 vs53 ± 38 hours, P< .001). No statistically significant change in SOFA score was found between groups 3 (1 - 6) vs2 (0 - 4), P= .17. No significant differences were found between study arms in ICU and hospital mortality, ICU and hospital LOS, ventilator free days, and PCT-c. Our results suggest that the combination of IV ascorbic acid, thiamine, and hydrocortisone significantly reduced the time to resolution of shock. Additional studies are needed to confirm these findings and assess any potential mortality benefit from this treatment. ClinicalTrials.gov; No.: NCT03422159; URL: www.clinicaltrials.gov.

What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials.

For more than half a century, low-density lipoprotein cholesterol (LDL-C) has been recognized as a major risk factor for incident atherosclerotic cardiovascular disease. The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9) in 2003, which prevents LDL-C receptor recycling, identified a new target for drug intervention. Recently, two large-scale randomized clinical outcomes trials involving fully human anti-PCSK9 monoclonal antibodies tested the hypothesis that targeting this pathway would reduce cardiovascular events. Both the FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) and ODYSSEY OUTCOMES trials met their primary efficacy endpoints, confirming findings reported earlier that major adverse cardiovascular events can be reduced by a further lowering of LDL-C beyond that achieved with statin therapy. In both trials, there were incremental reductions in LDL-C of > 50% from baseline, with no major safety concerns, over the trials’ median follow-up time (2.2 and 2.8 years, respectively). While there were differences in design, lipid management and overall results, key messages from both studies were similar. However, post-publication, additional questions have arisen, especially regarding drug effects over the long-term, including a potential mortality benefit.

Abstract TMP51: A VA Observational Study Examining the Mortality Benefit of Various Post-ischemic Stroke/tia Hypertension Goals - Is There a Too Low?

Introduction: Joint National Committee (JNC)-8 goal blood pressure (BP) recommendation of &lt; 140/90 mmHg has been supplanted by 2017 ACC/AHA goal of &lt; 130/80 mmHg for patients with ischemic stroke/TIA. Understanding potential mortality benefit for patients reaching ACC/AHA goal is needed. Hypothesis: Stroke/TIA patients reaching ACC/AHA goal BP will experience lower 1-year all-cause mortality compared to those reaching JNC-8 BP goals. Methods: This is a retrospective cohort of Veterans with stroke/TIA (N=39,053) who received their longitudinal outpatient primary care within a Veterans Administration Medical Center between 10/2014 and 9/2018. Patients were excluded (n=25,381) if they had missing or physiologically improbable BP values, died, or had less than 1 year of follow-up for analysis of 1-year mortality. We calculated average SBP during 90 days after discharge and assessed it in categorical form (≤115 mmHg, 106-115 mmHg, 116-130, mmHg, 131-140 mmHg, and &gt;140 mmHg) and continuous form. Multivariate COX proportional hazard regression was used to examine the relationship between average SBP groups and time to mortality 90 days after discharge up to 1 year. In multivariate logistic regression, we used continuous SBP along with its quadratic term to predict 1-year mortality. Results: A total of 12,337 eligible patients were included in the final analysis. COX proportional regression demonstrated a statistically significant higher risk of death among patients with SBP lower than 105 mmHg as compared to those with &gt; 140 mmHg (HR = 1.79, 95% CI= 1.37-2.34), but no statistical differences were found in other SBP groups. Predicted probability of 1-year mortality generated from the logistic regression was plotted and showed a “U” shaped relationship between SBP and mortality, whereas SBP ranges encompassing both AHA/ACC and JNC-8 goal BP recommendations are found on the “flat” part of the curve. Conclusions: In considering BP reached by 90-days, there was no differential 1-year all-cause mortality benefit between JNC-8 and ACC/AHA BP recommendations, whereas patients experiencing low SBPs were at increased risk for higher mortality. Providers should be aware of the association between lower SBP and higher mortality when treating BP.

The effect of beta-blockers on mortality in patients with heart failure and atrial fibrillation: A meta-analysis of observational cohort and randomized controlled studies

Beta-blockers (BB) are the cornerstone of therapy for heart failure (HF); however, the effects of these drugs on the prognosis of patients with concomitant atrial fibrillation (AF) remain controversial. The objective of this meta-analysis was to evaluate the efficacy of BB on mortality in HF coexisting with AF. A systematic search of PubMed, Embase and the Cochrane Library databases was conducted. Observational cohort studies and randomized controlled trials reporting outcomes of mortality or HF hospitalizations for patients with HF and AF, being assigned to BB treatment. A non-BB group was also included. A total of 8 clinical studies (5 randomized controlled trials and 3 observational cohort studies) involving 34197 patients were included in the analysis. The pooled analysis demonstrated that BB treatment was associated with a 22% reduction in relative risk of all-cause mortality in patients with HF and AF (RR: 0.78; 95% CI 0.71-0.86; p < 0.00001; I2 = 27%). The pooled analysis of 5 studies reported the outcome of HF hospitalization (2774 patients) which showed that BB therapy was not associated with a reduction of HF hospitalizations (RR: 0.94; 95% CI 0.79-1.11; p = 0.46; I2 = 38%). Meta-analysis suggests the potential mortality benefit of BB in patients with HF and AF. It was concluded herein that it is premature to deny patients with AF and HF to receive BB therapy considering current evidence.

Percutaneous Endoscopic Gastrostomy After Cardiothoracic Surgery in Children Less Than 2 Months Old: An Assessment of Long-Term Malnutrition Status and Gastrostomy Outcomes.

Infants with critical congenital heart disease undergoing cardiothoracic surgery commonly experience chronic malnutrition and growth failure. We sought to determine whether placement of a percutaneous endoscopic gastrostomy was associated with reduced moderate-severe malnutrition status and to describe percutaneous endoscopic gastrostomy-related clinical and safety outcomes in this population. Single-center, retrospective cohort study. Two hundred fifty-nine-bed, tertiary care, pediatric referral center. Children with congenital heart disease less than 2 months old undergoing cardiothoracic surgery from 2007 to 2013 with and without percutaneous endoscopic gastrostomy. None. Primary outcomes were weight for age z scores during hospitalization, at 6 months, and 1 year after cardiothoracic surgery. Secondary outcomes were frequency of percutaneous endoscopic gastrostomy revision, percutaneous endoscopic gastrostomy complications, and mortality. Statistical analyses included Wilcoxon rank-sum, Fisher exact, and Student t tests. Two hundred twenty-two subjects met study criteria, and 77 (35%) had percutaneous endoscopic gastrostomy placed at a mean of 45 ± 31 days after cardiothoracic surgery. No differences were noted for demographics, comorbidities, and weight for age z score at birth and at the time of cardiothoracic surgery. The percutaneous endoscopic gastrostomy cohort had greater Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery risk category (4 [4-5] vs 4 [2-4]) and length of stay (71 d [49-101 d] vs 26 d [15-42 d]). Mean weight for age z score at the time of percutaneous endoscopic gastrostomy was -2.8 ± 1.3. Frequency of moderate-severe malnutrition (weight for age z score, ≤ -2) was greater in children with percutaneous endoscopic gastrostomy at discharge (78% vs 48%), 6 months (61% vs 16%), and 1 year (41% vs 2%). Index mortality was lower in children with percutaneous endoscopic gastrostomy at 30 days (8% vs 0%) and hospital discharge (19% vs 4%). However, no mortality differences were observed after discharge. Growth velocity after percutaneous endoscopic gastrostomy was greater (44 ± 19 vs 10 ± 9 g/d). Children tolerated percutaneous endoscopic gastrostomy without hemodynamic compromise, minor percutaneous endoscopic gastrostomy complications, and anticipated percutaneous endoscopic gastrostomy revisions. Children without mortality had percutaneous endoscopic gastrostomy removal at a median duration of 253 days (133-545 d). Children with univentricular physiology had improved in-hospital mean growth velocity (6.3 vs 24.4 g/d; p < 0.01) and reduced 1-year rate moderate-severe malnutrition (66.7% vs 36.9%; p < 0.01) after percutaneous endoscopic gastrostomy placement. Percutaneous endoscopic gastrostomy placement was well tolerated and associated with improved postoperative growth velocity in children with critical congenital heart disease undergoing cardiothoracic surgery less than 2 months old. These findings were also noted in our subanalysis of children with univentricular physiology. Persistent rates of moderate-severe malnutrition were noted at 1-year follow-up. Although potential index mortality benefit was observed, definitive data are still needed.

Potential effect of age of BCG vaccination on global paediatric tuberculosis mortality: a modelling study

SummaryBackgroundBCG has been recommended at birth in countries with a high tuberculosis burden for decades, yet delayed vaccination is widespread. To support a WHO guidance review, we estimated the potential global tuberculosis mortality benefit of administering BCG on time and consequences of later administration.MethodsWe estimated age-specific BCG coverage in 152 high-burden countries using data from large, nationally representative household surveys, to parameterise a static mathematical model, calibrated to global childhood tuberculosis deaths in 2016. 12 hypothetical scenarios explored the effect of BCG delivery at birth, 6 weeks, 6 months, or 9–12 months, on tuberculosis deaths per global birth cohort by age 15 years, including delivery at the time of the first diphtheria–tetanus–pertussis vaccine (DTP1) or the first measles-containing vaccine (MCV1). We assumed constant vaccine efficacy by age, but varied coverage and degree of vaccination delay, including no delay.FindingsIn 152 high-burden countries, we estimated that BCG coverage in 2016 was 37% at 1 week of age, 67% at 6 weeks, and 92% at 3 years. Modelled scenarios in which 92% BCG coverage was achieved at birth reduced tuberculosis deaths in the global birth cohort by 5449 (95% uncertainty range 218–15 071) or 2·8% (0·1–7·0) by age 15 years. 100% coverage at birth reduced tuberculosis deaths by 16·5% (0·7–41·9). Later administration increased tuberculosis deaths—eg, BCG vaccination at 6 weeks, the recommended age of DTP1, increased tuberculosis deaths by 0·2% (0–0·4), even if BCG reached DTP1 coverage levels (94% at 3 years).InterpretationReducing delays and increasing coverage at birth would substantially reduce global paediatric tuberculosis mortality. Modelled scenarios whereby BCG was administered later in the infant schedule were all estimated to increase tuberculosis deaths, even with increased coverage. The WHO recommendation for BCG at birth should be maintained and emphasised.FundingWHO.

Whole-Body CT after Motor Vehicle Crash: No Benefit after High-Energy Impact and with Normal Physical Examination

Performing a whole body computerized tomography (CT) scan after a motor vehicle crash (MVC) when the physical exam suggests no new injury remains a source of debate. It remains a common practice despite prospective evidence of no reduction in mortality. Prior retrospective studies have shown a potential mortality benefit of whole-body CT following these traumas compared to selective scanning, but the overall quality of evidence is lacking. Proponents argue that whole-body CT finds more injuries and injuries that may have been missed on exam, but it comes with the cost of radiation exposure, possible adverse effects of iodine contrast, and added expense. The Vittel criteria, originally used for field triage, now guide whole-body CT decisions in France. The Vittel criteria include physiologic variables, kinetic components or mechanism of injury, injuries sustained, and resuscitation required. Use of these criteria as an indication to perform whole-body CT has lacked specificity. Investigators in this retrospective study hypothesized that patients involved in an MVC with a GCS of 15, a normal exam of the torso, and only a kinetic component of the Vittel criteria, whole-body CT is not indicated.

Update on screening for lung cancer.

As the leading cause of cancer related death world wide, lung cancer is responsible for an enormous amount of suffering and disability. Detection of disease when it is surgically curable is associated with far greater odds of cure, and therefore it is a disease for which mass screening of high-risk populations has significant potential benefit. Starting in 2011, with the publication of the National Lung Screening Trial from United States (U.S.), mass screening programs have emerged throughout the U.S., as well as in other countries. More recently, large European screening trials have confirmed the potential mortality benefit of lung cancer screening. This invited non-systematic review paper covers the trial that data justify mass-screening, for lung cancer and proposes strategies for maximizing benefits and minimizing harms in the context of a mass public health lung cancer screening program.

Total Body Skin Examination Practices: A Survey Study Amongst Dermatologists at High-Risk Skin Cancer Clinics.

Although total body skin examination (TBSE) is the primary screening mechanism for melanoma, there is no consensus on which anatomic sites a screening TBSE should include. We sought to establish which anatomic sites are examined during routine (>90%) TBSEs of patients at high risk for skin cancer. A Google survey was emailed to 173 international dermatologist skin cancer specialists. More than 75% of participants reported routinely examining the scalp, ears, face and neck, trunk, breasts, inframammary areas, axillae, extremities, palms and soles, nails, interdigital spaces, and buttocks. The least frequently inspected anatomic sites included genitalia, with male genitalia more frequently examined than female (penis n = 39; 52%; labia majora n = 21; 28%; P = 0.003), the perianal region (n = 26; 34.7%), and the ocular conjunctiva and oral mucosa (n = 35; 46.7%). Participants cited not screening these areas because of perceived patient discomfort, low prevalence of malignancy, and the expectation that other specialists examine the area. The role of routine surveillance of neglected anatomic sites is unclear and warrants further discussion weighing potential mortality benefit against the incidence of melanoma in obscure sites, morbidity of intervention in sensitive sites, cost-effectiveness, and potential for patient discomfort.

The Role of Percutaneous Coronary Intervention in the Treatment of Chronic Total Occlusions: Rationale and Review of the Literature.

Chronic total occlusion (CTO) of a coronary artery is defined as an occluded segment with no antegrade flow and a known or estimated duration of at least 12 weeks. We considered the current literature describing the indications and clinical outcomes for denovo CTO- percutaneous coronary intervention (PCI), and discuss the role of CTO-PCI and future directions for this procedure. Databases (PubMed, the Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL were searched and relevant studies of CTO-PCI were selected for review. The prevalence of coronary artery CTO's has been reported to be ~ 20% among patients undergoing diagnostic coronary angiography for suspected coronary artery disease. Revascularization of any CTO can be technically challenging and a time-consuming procedure with relatively low success rates and may be associated with a higher incidence of complications, particularly at non-specialized centers. However, with an increase in experience and technological advances, several centers are now reporting success rates above 80% for these lesions. There is marked variability among studies in reporting outcomes for CTO-PCI with some reporting potential mortality benefit, better quality of life and improved cardiac function parameters. Anecdotally, properly selected patients who undergo a successful CTO-PCI most often have profound relief of ischemic symptoms. Intuitively, it makes sense to revascularize an occluded coronary artery with the goal of improving cardiovascular function and patient quality of life. CTO-PCI is a rapidly expanding specialized procedure in interventional cardiology and is reasonable or indicated if the occluded vessel is responsible for symptoms or in selected patients with silent ischemia in whom there is a large amount of myocardium at risk and PCI is likely to be successful.