Articles from Other Journals

Rick Robbins, M.D. Rick Robbins, M.D.

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Butler CC, Gillespie D, White P, et al. N Engl J Med. 2019 Jul 11;381(2):111-120. [CrossRef] [PubMed]

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce use of antibiotics in patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). The authors performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The authors conclude that CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.

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Rick Robbins, M.D. Rick Robbins, M.D.

Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial

Subirà C, Hernández G, Vázquez A. et al. JAMA. 2019;321(22):2175-2182. [CrossRef]

Daily spontaneous breathing trials (SBTs) are the best approach to determine whether patients are ready for disconnection from mechanical ventilation, but mode and duration of SBT remain controversial. The authors randomized patients to undergo a 2-hour T-piece SBT (n = 578) or a 30-minute SBT with 8-cm H2O pressure support ventilation (n = 557). Among 1153 patients who were randomized successful extubation occurred in 473 patients (82.3%) in the pressure support ventilation group and 428 patients (74.0%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13.0%; P = .001). Reintubation, median intensive care unit length of, and median hospital length of stay did not differ but hospital mortality was lower for pressure support (10.4% vs 14.9%, P = .02) as was 90-day mortality was (13.2% vs 17.3%, P = .04). The authors conclude that among patients receiving mechanical ventilation, a spontaneous breathing trial consisting of 30 minutes of pressure support ventilation, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for spontaneous breathing trials.

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Rick Robbins, M.D. Rick Robbins, M.D.

Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis

Seymour CW, Kennedy JN, Wang S, et al. JAMA. 2019 May 19. [CrossRef] [PubMed]

Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. The authors derived sepsis phenotypes from 20,189 total who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients), in a prospective cohort study of sepsis due to pneumonia. Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. The 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). This study shows that older sicker patients with sepsis are more likely to die. The authors conclude that further research is needed to determine the utility of these phenotypes in clinical care.  

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Rick Robbins, M.D. Rick Robbins, M.D.

Association of Unrecognized Obstructive Sleep Apnea with Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery

Chan MTV, Wang CY, Seet E, et al. JAMA. 2019 May 14;321(18):1788-98. [CrossRef] [PubMed]

Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. This prospective cohort study enrolled adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate or mild OSA (P > .05). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

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Rick Robbins, M.D. Rick Robbins, M.D.

CPAP Adherence May Slow 1-Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea

Richards KC, Gooneratne N, Dicicco B, et al. J Am Geriatr Soc. 2019 Mar;67(3):558-64. [CrossRef] [PubMed]

Obstructive sleep apnea (OSA) has been linked to an increased risk for Alzheimer's disease (AD), but little prospective evidence exists on the effects of OSA treatment in preclinical AD. The objective was to determine if continuous positive airway pressure (CPAP) treatment adherence, controlling for baseline differences, predicts cognitive and everyday function after 1 year in older adults with mild cognitive impairment (MCI) and to determine effect sizes for a larger trial. Older adults, aged 55 to 89 years, with an apnea-hypopnea index of 10 or higher participated: (1) MCI, OSA, and CPAP adherent (MCI +CPAP), n = 29; and (2) MCI, OSA, CPAP nonadherent (MCI -CPAP), n = 25. The primary cognitive outcome was memory (Hopkins Verbal Learning Test-Revised), and the secondary cognitive outcome was psychomotor/cognitive processing speed (Digit Symbol subtest from the Wechsler Adult Intelligence Scale Substitution Test). Secondary function and progression measures were the Everyday Cognition, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale, and Clinical Dementia Rating. Statistically significant improvements in psychomotor/cognitive processing speed in the MCI +CPAP group vs the MCI -CPAP group were observed at 1 year after adjustment for age, race, and marital status (parameter estimate = 1.68; standard error = 0.47; 95% confidence interval = 0.73-2.62), with a 6-month effect size (ES) of 0.46 and a 1-year ES of 1.25. There were small to moderate ESs for memory (ES 0.20, 6 mo), attention (ES 0.25, 1 y), daytime sleepiness (ES 0.33, 6 mo and ES 0.22, 1 y), and everyday function (ES 0.50, 6 mo) favoring the MCI +CPAP group vs the MCI -CPAP group. The authors conclude that after controlling for baseline differences, 1 year of CPAP adherence in MCI +OSA significantly improved cognition and may slow the trajectory of cognitive decline.

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Rick Robbins, M.D. Rick Robbins, M.D.

Almost Half of Physicians Say EHRs Have Hurt Quality of Care

Frellick M. Medscape. May 01, 2019. Available at: https://www.medscape.com/viewarticle/912340 (accessed 5/2/19)

Recently, Medscape conducted a poll titled “What Are the Pros and Cons of Your EHR?”. There were 273 respondents — 207 physicians and 66 nurses/APRNs. More physicians said that electronic health record (EHR) systems have decreased quality of care (44%) in their primary workplace than increased it (40%). Nurses and advanced practice registered nurses (APRNs) saw more benefit than detriment in EHRs: 42% said they had increased quality of care vs 35% who said they had decreased care quality.

A clue to the cause for the perception of a decrease in quality may be that few physicians or nurses were involved in the decision of which EHR to use in their primary workplace. Among physicians, only 28% had input in choosing the HER and only 2% of physicians, nurses, and APRNs said they had input into the decision and the system they wanted was chosen.

When asked what aspects of EHRs increased quality of care, the top answer among physicians was the ability to locate and review patient information more easily (59%), followed by the ability to electronically subscribe (49%), and portability/access to patient records by all members of the care team (44%). Portability and access by all on the team was the top reason given by nurses/APRNs for increases of care quality (62%), followed by ability to locate and review patient information more easily (60%), and ability to electronically prescribe (46%).

When physicians and nurses/APRNs were asked what aspects of EHRs decrease quality of care, they gave similar weight to these four reasons: added paperwork/charting; entering data during the patient encounter; lack of interoperability with other systems; and system failures or problems. A family medicine physician summarized what many doctors have said the field of medicine has lost in a decade with such a system — the nuances in narratives about the patient. They reduce "fascinating human stories to utterly boring, repetitious templates," he wrote.

The results of the iCOMPARE reported earlier this month suggest that the drift from face-to-face care is continuing with the next generation of physicians. First-year residents spend almost five times more hours on indirect patient care than on face-to-face patient care, and most of that time was spent working with EHRs.

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Rick Robbins, M.D. Rick Robbins, M.D.

Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial

Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Am J Respir Crit Care Med. 2019 Feb 1. [Epub ahead of print] [CrossRef][PubMed]

A vocal minority of researchers have advised against delaying vasopressors in septic shock, arguing that norepinephrine, not intravenous fluid, as the most effective initial treatment to correct the loss of vascular tone ("vasoplegia") from septic shock. The authors conducted a Phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults sepsis with hypotension increases shock control by six hours compared with standard care. This single-center, randomized, double-blind, placebo-controlled clinical trial was conducted at Siriraj Hospital, Bangkok, Thailand and enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n=155) and standard treatment (n=155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure >65mmHg, with urine flow >0.5mL/kg/h for 2 consecutive hours, or decreased serum lactate >10% from baseline) by 6 hours after diagnosis. The patients in both groups were well matched in background characteristics and disease severity. Median time from emergency room arrival to norepinephrine administration was significantly shorter in early norepinephrine group (93 vs.192 min; P<0.001). Shock control rate by 6 hours was significantly higher in early norepinephrine group (118/155 [76.1%] vs.75/155 [48.4%]; P<0.001). 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P=0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P=0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P=0.03). The authors conclude that early norepinephrine was significantly associated with increased shock control by 6 hours. A much larger U.S-based trial testing early vasopressors in septic shock (CLOVERS) is currently recruiting, with plans to enroll up to 2,300 patients and an expected completion date of June 2021.

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Rick Robbins, M.D. Rick Robbins, M.D.

Association of Positive Airway Pressure Prescription with Mortality in Patients with Obesity and Severe Obstructive Sleep Apnea: The Sleep Heart Health Study

Lisan Q, Van Sloten T, Marques Vidal P, Haba Rubio J, Heinzer R, Empana JP. JAMA Otolaryngol Head Neck Surg. 2019 Apr 11. [Epub ahead of print] [CrossRef] [PubMed]

The association of positive airway pressure (PAP) with reduced mortality in patients with obstructive sleep apnea (OSA) remains uncertain. This European, NIH-funded, multicenter, population-based cohort study evaluated data from the Sleep Heart Health Study (SHHS), a long-term observational cohort study that included participants between 1995 and 1998, with a mean follow-up of 11.1 years. Analyses were performed in September 2018. Within the SHHS, we compared patients with obesity and severe OSA with (n = 81) and without (n = 311) prescription of PAP therapy, after matching patients from each group by age, sex, and apnea-hypopnea index. Of 392 study participants, 316 (80.6%) were men, and mean (SD) age was 63.1 (11.0) years. Ninety-six deaths occurred; 12 among the prescribed-PAP group and 84 among the nonprescribed-PAP group, yielding crude incidence rates of 12.8 vs 24.7 deaths per 1000 person-years. In Cox multivariate analysis, the hazard ratio (HR) of all-cause mortality for prescribed PAP therapy was 0.38 (95% CI, 0.18-0.81). After propensity matching, the HR of all-cause mortality for prescribed PAP therapy was 0.58 (95% CI, 0.35-0.96). According to survival curves, the difference in mortality appears 6 to 7 years after initiation of PAP therapy. The authors concluded that positive airway pressure prescription is associated with reduced all-cause mortality, and this association appears several years after PAP initiation. If replicated, these findings may have strong clinical implications.

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Rick Robbins, M.D. Rick Robbins, M.D.

Effect of Glucose Improvement on Spirometric Maneuvers in Patients with Type 2 Diabetes: The Sweet Breath Study

Gutiérrez-Carrasquilla L, Sánchez E, Barbé F, et al. Diabetes Care. 2019 Apr;42(4):617-24. [CrossRef] [PubMed]

 The authors conducted a prospective interventional study to determine if an improvement in glycemic control affects pulmonary function. Sixty patients with type 2 diabetes and forced expiratory volume in 1 s (FEV1) <90% of predicted were studied. Spirometry was performed at baseline and after a 3-month period in which antidiabetic therapy was intensified. Those with an HbA1c reduction of >0.5% were considered to be good responders (n = 35). Good responders exhibited a significant improvement in spirometric values between baseline and the end of the study (forced vital capacity [FVC]: 78.5 + 12.6% vs. 83.3 + 14.7%, P = 0.029]; FEV1: 75.6 + 15.3% vs. 80.9 + 15.4%, P = 0.010; and peak expiratory flow [PEF]: 80.4 6 21.6% vs. 89.2 6 21.0%, P = 0.007). However, no changes were observed in the group of nonresponders when the same parameters were evaluated (P = 0.586, P = 0.987, and P = 0.413, respectively). Stepwise multivariate regression analysis showed that the absolute change in HbA1c independently predicted increased FEV1 (R2 = 0.175) and PEF (R2 = 0.323). In contrast, the known duration of type 2 diabetes, but not the amelioration of HbA1c, was related to changes in forced expiratory flow between 25% and 75% of the FVC. In type 2 diabetes, spirometric measurements reflecting central airway obstruction and explosive muscle strength exhibit significant amelioration after a short improvement in glycemic control. The reason for the nonsignificant improvement in spirometry with improved type 2 diabetes control was unclear.  

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Rick Robbins, M.D. Rick Robbins, M.D.

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

Mak ACY, White MJ, Eckalbar WL, et al. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1552-64. [CrossRef] [PubMed]

Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. However, there are significant racial/ethnic differences in albuterol drug response. The authors performed whole-genome sequencing pharmacogenetics study from 1,441 children with asthma to identify genetic association with bronchodilator response (BDR). They identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10−7) and suggestive (P < 7.06 × 10−6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. This study demonstrates that a set of genetic mutations found mostly in children of African-American or Puerto Rican descent may make them less likely to respond to albuterol. This research suggests that a genetic test could be developed to help identify patients who are resistant to albuterol and could benefit from alternative treatments.

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Rick Robbins, M.D. Rick Robbins, M.D.

Patient Safety Outcomes under Flexible and Standard Resident Duty-Hour Rules and Sleep and Alertness in a Duty-Hour Flexibility Trial in Internal Medicine

Silber JH, Bellini LM, Shea JA, et al. N Engl J Med 2019; 380:905-14. [CrossRef]

Basner M, Asch DA, Shea JA, et al. N Engl J Med 2019; 380:915-23. [CrossRef] [PubMed]

In 2003 the American Council on Graduate Medical Education (ACGME) limited resident work-hour limits. In 2011 the ACGME enacted even more stringent requirements. However, waivers were granted allowing some flexibility in shift length, as well as time off between shifts; caps on weekly hours worked, total days off, and the frequency of overnight call were maintained. Some argued that there was a paucity of evidence to support these changes and some new risks, such as those associated with increased handoffs of care or inadequate educational exposure. The Arizona Thoracic Society was amongst those who urged the ACGME to conduct randomized trials. In today’s edition of the New England Journal the results of two of these trials are reported.

The first report used Medicare claims data to assess patient outcomes. Mortality, readmissions and payments did not differ in programs with flexible hours worked standard hours. The second study found that sleep duration also did not differ in flexible programs as compared with standard programs, with interns in both groups averaging approximately 7 hours of sleep per night. Essentially, interns made up for lost sleep on extended shifts by sleeping more during time off.

A thoughtful editorial by Rosenbaum and Lamas summarizes the data and points out that there may be some downsides to the resident hour restrictions including increased handoffs of care or inadequate educational exposure.

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Rick Robbins, M.D. Rick Robbins, M.D.

Factors Associated with High-Quality Guidelines for the Pharmacologic Management of Chronic Diseases in Primary Care: A Systematic Review

Molino CGRC, Leite-Santos NC, Gabriel FC, et al. JAMA Intern Med. 2019 Feb 18. [Epub ahead of print] [CrossRef] [PubMed]

The authors assessed 421 clinical practice guidelines (CPGs) in primary care using the validated Appraisal of Guidelines for Research and Evaluation Instrument, version II (AGREE-II) tool. A multiple logistic regression was performed to identify factors associated with quality of CPGs. Of the CPGs reviewed only 23.5% (99) were classified as high quality. Factors associated with high-quality CPGs included having more than 20 authors (odds ratio, 9.08; 95%CI, 3.35-24.62), development at governmental institutions (odds ratio, 10.38; 95%CI, 2.72-39.60), and reporting funding (odds ratio, 10.34; 95%CI, 4.77-22.39). Year of publication, region, guideline version, and scope were not associated with quality among included CPGs. An accompanying editorial discusses the implications of the study and argues that only high quality guidelines should be implemented. The study agrees with previous publications examining the quality of non-primary care guidelines including the Infectious Disease Society of America and American Thoracic Society by Lee et al. in 2011 and several publications in the SWJPCC examining ICU guidelines.

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Rick Robbins, M.D. Rick Robbins, M.D.

Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free from Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Beitler JR, Sarge T, Banner-Goodspeed VM, et al. JAMA. 2019 Feb 18. [Epub ahead of print] [CrossRef] [PubMed]

Shortly after ARDS was described the beneficial effects of PEEP on oxygenation were discovered. However, PEEP can have deleterious effects.  Despite many proposed measures and methods, how to adjust the pressure to the “optimal” level has remained elusive. This multicenter study sought to determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes. PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. The authors conclude that these findings do not support PES-guided PEEP titration in ARDS. A thoughtful editorial accompanies the manuscript in the same issue of JAMA.

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Rick Robbins, M.D. Rick Robbins, M.D.

Prevalence, Underlying Causes, and Preventability of Sepsis-Associated Mortality in US Acute Care Hospitals

Rhee C, Jones TM, Hamad Y, et al. JAMA Netw Open. 2019 Feb 1;2(2):e187571. [CrossRef] [PubMed]

Sepsis affects nearly 270,000 Americans each year and has a mortality risk of 30% to 60%. Nearly one in three patients who die in the hospital have sepsis, according to the Centers for Disease Control and Prevention and has been targeted as a preventable hospital-acquired infection by the Centers for Medicare and Medicaid Services. However, the extent to which sepsis is preventable, is unknown.

The authors conduced a retrospective cohort study of 568 randomly selected adults admitted to 6 US academic and community hospitals who died in the hospital or were discharged to hospice and not readmitted. The preventability of each sepsis-associated death was rated on a 6-point Likert scale.

Sepsis was present in 300 of the 568 subjects and was the immediate cause of death in 198 cases. The next most common immediate causes of death were progressive cancer (92) and heart failure (39). Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths. However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable.

The authors conclude that in this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care.

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Rick Robbins, M.D. Rick Robbins, M.D.

Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial

Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Am J Respir Crit Care Med. 2019 Feb 1 [Epub ahead of print]. [CrossRef] [PubMed]

The authors conducted a single-center, randomized, double-blind, placebo-controlled clinical trial was conducted in Bangkok, Thailand. The study enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n=155) and standard treatment (n=155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure >65mmHg, with urine flow >0.5mL/kg/h for 2 consecutive hours, or decreased serum lactate >10% from baseline) by 6 hours after diagnosis. Shock control rate by 6 hours was significantly higher in early norepinephrine group (118/155 [76.1%] vs.75/155 [48.4%]; P<0.001). 28-day mortality was not different between groups: 24/155(15.5%) in the early norepinephrine group versus 34/155(21.9%) in the standard treatment group (P=0.15). The authors conclude that further studies are needed to determine if early norepinephrine is associated with better outcomes such as mortality, ICU and hospital stay, etc.

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Rick Robbins, M.D. Rick Robbins, M.D.

A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy

Hajek P, Phillips-Waller A, Przulj D, et al. N Engl J Med. 2019 Jan 30. [Epub ahead of print]. [CrossRef] [PubMed]

E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine or other products approved as smoking-cessation treatments. The authors randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). The authors conclude that E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. Since 80% of those in the e-cigarette group that quit smoking continued to use e-cigarettes after 1 year, the long-term health benefits remain unclear.

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Rick Robbins, M.D. Rick Robbins, M.D.

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

Krag M, Marker S, Perner A, et al. N Engl J Med. 2018 Dec 6;379(23):2199-2208. [CrossRef] [PubMed]

Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. A recent meta-analysis suggested that proton-pump inhibitors result in a decrease in gastrointestinal bleeding but an increase in pneumonia. In this European, multicenter, parallel-group, blinded trial, adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding were randomly assigned to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo. The primary outcome was death by 90 days after randomization. A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. The authors conclude that the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo.

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Rick Robbins, M.D. Rick Robbins, M.D.

Comparison of Wait Times for New Patients Between the Private Sector and United States Department of Veterans Affairs Medical Centers

Penn M, Bhatnagar S, Kuy S, Lieberman S, Elnahal S, Clancy C, Shulkin D. JAMA Netw Open. 2019 Jan 4;2(1):e187096. [CrossRef] [PubMed]

Concerns have been raised about the adequacy of health care access among patients cared for within the United States Department of Veterans Affairs (VA) health care system. The authors determined wait times for new patients receiving care at VA medical centers and compare wait times in the VA medical centers with wait times in the private sector (PS). A retrospective, repeated cross-sectional study was conducted of new appointment wait times for primary care, dermatology, cardiology, or orthopedics at VA medical centers in 15 major metropolitan areas in 2014 and 2017. Comparison data from the PS came from a published survey that used a secret shopper survey approach. Secondary analyses evaluated the change in overall and unique patients seen in the entire VA system and patient satisfaction survey measures of care access between 2014 and 2017. The outcome of interest was patient wait time. Wait times in the VA were determined directly from patient scheduling. Wait times in the PS were as reported in Merritt Hawkins surveys using the secret shopper method. Compared with the PS, overall mean VA wait times for new appointments in 2014 were similar (mean [SD] wait time, 18.7 [7.9] days PS vs 22.5 [7.3] days VA; P = .20). Department of Veterans Affairs wait times in 2014 were similar to those in the PS across specialties and regions. In 2017, overall wait times for new appointments in the VA were shorter than in the PS (mean [SD], 17.7 [5.9] vs 29.8 [16.6] days; P < .001). This was true in primary care (mean [SD], 20.0 [10.4] vs 40.7 [35.0] days; P = .005), dermatology (mean [SD], 15.6 [12.2] vs 32.6 [16.5] days; P < .001), and cardiology (mean [SD], 15.3 [12.6] vs 22.8 [10.1] days; P = .04). Wait times for orthopedics remained longer in the VA than the PS (mean [SD], 20.9 [13.3] vs 12.4 [5.5] days; P = .01), although wait time improved significantly between 2014 and 2017 in the VA for orthopedics while wait times in the PS did not change (change in mean wait times, increased 1.5 days vs decreased 5.4 days; P = .02). Secondary analysis demonstrated an increase in the number of unique patients seen and appointment encounters in the VA between 2014 and 2017 (4 996 564 to 5 118 446, and 16 476 461 to 17 331 538, respectively), and patient satisfaction measures of access also improved (satisfaction scores increased by 1.4%, 3.0%, and 4.0% for specialty care, routine primary care, and urgent primary care, P < .05). The authors conclude that although wait times in the VA and PS appeared to be similar in 2014, there have been interval improvements in VA wait times since then, while wait times in the PS appear to be static. These findings suggest that access to care within the VA has improved over time.

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Rick Robbins, M.D. Rick Robbins, M.D.

The Importance of Smoking Cessation on Surgical Outcome in Primary Lung Cancer

Fukui M, Suzuki K, Matsunaga T, Oh S, Takamochi K. Ann Thorac Surg. 2019 Jan 2. pii: S0003-4975(18)31871-X. [CrossRef] [PubMed] 

Smoking cessation is important in the management of patients who require pulmonary resection. However, the impact of short-term smoking cessation on the surgical outcome remains unclear. The authors conducted a retrospective study was conducted on patients with stage I-III primary lung cancer who underwent resection between 2012 and 2016. The rate of surgical mortality and morbidity were evaluated according to smoking status. The relationship between the preoperative interval of smoking cessation and pulmonary complications after surgery was also examined. The study included 666 patients, of which 256 (38.4%) were never smokers and 410 (61.6%) were smokers. There were significant differences between the smokers and never smokers regarding the 90-day mortality rate (2.0% vs 0%, p=0.025), and respiratory complications (22.3% vs 3.5%, p<0.001). A multivariate analysis indicated that smoking (OR 2.8, p = 0.017), FEV 1.0/ FVC < 0.7 (OR 2.6, p = 0.001), %DLCO < 40% (OR 4.2, p =<0.001), and clinical stage of lung cancer (OR 2.3, p = 0.005) were predictors of pulmonary complications after pulmonary resection. In comparison to never smokers, the odds ratios for pulmonary complications at each cessation interval (Current smoker/ cessation for -1month/ 1-3 months/ 3-6 months/ 6-12 months/ > 12 months) were 12.9 (p < 0.001)/ 10.3 (p < 0.001)/ 8.5 (p < 0.001)/ 6.3 (p=0.011)/ 6.0 (p = 0.003)/ 5.0 (p < 0.001). A longer period of cessation might be more effective for reducing the risk of pulmonary complications, however, even short-term smoking cessation is beneficial prior to thoracotomy for lung cancer.

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Rick Robbins, M.D. Rick Robbins, M.D.

FDA Warns About Increased Risk of Ruptures or Tears in the Aorta Blood Vessel With Fluoroquinolone Antibiotics in Certain Patients

US Food and Drug Administration. December 20, 2018. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm (accessed 12/22/18).

A U.S. Food and Drug Administration (FDA) review found that fluoroquinolones can increase the occurrence of aortic aneurysm dissection or rupture. Cases and four published observational studies showed an increased risk of aortic aneurysm or dissection associated with fluoroquinolone use. The FDA advises prescribing fluoroquinolone antibiotics to patients who have an aortic aneurysm or are at risk for an aortic aneurysm, such as patients with peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients unless no other alternatives are available. The reports are not surprising since fluoroquinolones have been associated tendon inflammation and even rupture. Azithromycin and doxycycline have also rarely been reported to cause tendonitis and rupture but it is unclear whether caution should be used with these antibiotics in patients at risk for aortic dissection or rupture.

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