Empowering telemetry technicians and enhancing communication to improve in-hospital cardiac arrest survival.

Delays in treatment of in-hospital cardiac arrests (IHCAs) are associated with worsened survival. We sought to assess the impact of a bundled intervention on IHCA survival in patients on centralised telemetry. A retrospective quality improvement study was performed of a bundled intervention which incorporated (1) a telemetry hotline for telemetry technicians to reach nursing staff; (2) empowerment of telemetry technicians to directly activate the IHCA response team and (3) a standardised escalation system for automated critical alerts within the nursing mobile phone system. In the 4-year study period, there were 75 IHCAs, including 20 preintervention and 55 postintervention. Cox proportional hazard regression predicts postintervention individuals have a 74% reduced the risk of death (HR 0.26, 95% CI 0.08 to 0.84) during a code and a 55% reduced risk of death (HR 0.45, 95% CI 0.23 to 0.89) prior to hospital discharge. Overall code survival improved from 60.0% to 83.6% (p=0.031) with an improvement in ventricular tachycardia/ventricular fibrillation (VT/VF) code survival from 50.0% to 100.0% (p=0.035). There was no difference in non-telemetry code survival preintervention and postintervention (71.4% vs 71.3%, p=0.999). The bundled intervention, including improved communication between telemetry technicians and nurses as well as empowerment of telemetry technicians to directly activate the IHCA response team, may improve IHCA survival, specifically for VT/VF arrests.

Results and lessons from a hospital-wide initiative incentivised by delivery system reform to improve infection prevention and sepsis care.

BACKGROUND: An academic safety-net hospital leveraged the federally funded state Delivery System Reform Incentive Payment programme to implement a hospital-wide initiative to reduce healthcare-associated infections (HAIs) and improve sepsis care. METHODS: The study period was from 2013 to 2017. The setting is a 770-bed urban hospital with six intensive care units and a large emergency department. Key interventions implemented were (1) awareness campaign and clinician engagement, (2) implementation of HAI and sepsis bundles, (3) education of clinical personnel using standardised curriculum on bundles, (4) training of key managers, leaders and personnel in quality improvement methods, and (5) electronic medical record-based clinical decision support. Throughout the 5-year period, staff received frequent, clear, visible and consistent messages from leadership regarding the importance of their participation in this initiative, performing hand hygiene and preventing potential regulatory failures. Several process measures including bundle compliance, hand hygiene and culture of safety were monitored. The primary outcomes were rates of central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI) and sepsis mortality. RESULTS: From 2013 to 2017, the hospital-wide rates of HAI reduced: CLABSI from 1.6 to 0.8 per 1000 catheter-days (Poisson regression estimate: -0.19; 95% CI -0.29 to -0.09; p=0.0002), CAUTI from 4.7 to 1.3 per 1000 catheter-days (-0.34; -0.43 to -0.26; p<0.0001) and SSI after 18 types of procedures from 3.4% to 1.3% (-0.29; -0.34 to -0.24; p<0.0001). Mortality of patients presenting to emergency department with sepsis reduced from 9.4% to 2.9% (-0.42; -0.49 to -0.36; p<0.0001). Adherence to bundles of care and hand hygiene and the hospital culture of patient safety improved. Results were sustained through 2019. CONCLUSION: A hospital-wide initiative incentivised by the Delivery System Reform Incentive Payment programme succeeded in reducing HAI and sepsis mortality over 5 years in a sustainable manner.

Sepsis at a Safety Net Hospital: Risk Factors Associated With 30-Day Readmission.

BACKGROUND: Sepsis is a leading cause of hospitalization, and subsequent readmissions are frequent and costly. There is an expanding body of literature describing risk factors for readmissions in patients with sepsis. However, there are little data studying medically underserved patients who typically receive their care at a safety net hospital. METHODS: In a retrospective cohort study, we evaluated 1355 sepsis survivors at risk of hospital readmission in fiscal year 2013 at a safety net hospital. We described patient characteristics during their initial and readmission hospitalizations and analyzed risk factors associated with 30-day readmission. RESULTS: The 30-day readmission rate among sepsis survivors was 22.6%. Comorbid conditions associated with readmissions included end-stage renal disease (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.17-1.36), malignancy (OR, 1.14; 95% CI, 1.08-1.21), and cirrhosis (OR, 1.11; 95% CI, 1.02-1.20). Bacteremia during the initial hospitalization (OR, 1.07; 95% CI, 1.01-1.15) and being discharged with a vascular catheter (OR, 1.10; 95% CI, 1.01-1.20) were associated with readmission. Less severe sepsis during the initial hospitalization was associated with a reduced risk of 30-day readmission (OR, 0.91; 95% CI, 0.87-0.94). CONCLUSIONS: At a safety net hospital, patients who survived their initial sepsis hospitalization had a 30-day readmission rate to our institution of 22.6% that is comparable to rates described in prior studies. Readmission was commonly due to infection. Factors associated with readmission included multiple comorbid medical conditions, bacteremia, and being discharged with a vascular catheter. Further studies in this population are needed to determine potential modifiability of these risk factors in an attempt to reduce sepsis readmissions.

An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002).

INTRODUCTION: PIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients. METHODS: Between August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics. RESULTS: At baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related. CONCLUSIONS: Long-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF. FUNDING: F. Hoffmann-La Roche Ltd./Genentech, Inc. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00080223. Plain language summary available for this article.

Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring progressive lung scarring. To elucidate the molecular basis of IPF, we performed exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden analysis comparing 78 European cases and 2,816 controls implicated PARN, an exoribonuclease with no previous connection to telomere biology or disease, with five new heterozygous damaging mutations in unrelated cases and none in controls (P = 1.3 × 10(-8)); mutations were shared by all affected relatives (odds in favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis congenita, harbored significantly more new damaging and missense variants at conserved residues in cases than in controls (P = 1.6 × 10(-6)). PARN and RTEL1 mutation carriers had shortened leukocyte telomere lengths, and we observed epigenetic inheritance of short telomeres in family members. Together, these genes explain ~7% of familial pulmonary fibrosis and strengthen the link between lung fibrosis and telomere dysfunction.

Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation.

BACKGROUND: Short telomere lengths are found in a subset of patients with idiopathic pulmonary fibrosis, but their clinical significance is unknown. Our aim was to investigate whether patients with various blood leucocyte telomere lengths had different overall survival. METHODS: In this observational cohort study, we enrolled patients with interstitial lung disease from Dallas, TX (primary cohort), and from Chicago, IL, and San Francisco, CA (replication cohorts). We obtained genomic DNA samples from unrelated healthy controls in Dallas, TX, and spouses of patients were also enrolled as an independent control group. Telomere lengths were measured in genomic DNA samples isolated from peripheral blood obtained at the time of the initial enrolment assessment. The primary endpoint was transplant-free survival (ie, time to death or lung transplantation) in the Dallas cohort. Findings were validated in the two independent idiopathic pulmonary fibrosis cohorts (Chicago and San Francisco). FINDINGS: 370 patients were enrolled into the Dallas cohort between June 17, 2003, and Aug 25, 2011. The 149 patients with idiopathic pulmonary fibrosis had shorter telomere lengths than did the 195 healthy controls (mean age-adjusted log-transformed ratio of telomere to single copy gene was -0.16 [SD 0.23] vs 0.00 [0.18]; p<0.0001); however, telomere lengths of the Dallas patients with idiopathic pulmonary fibrosis (1.33 [SD 0.25]) were similar to the 221 patients with other interstitial lung disease diagnoses (1.46 [0.24]) after adjusting for age, sex, and ethnicity (p=0.47). Telomere length was independently associated with transplant-free survival time for patients with idiopathic pulmonary fibrosis (HR 0.22 [95% CI 0.08-0.63]; p=0.0048), but not for patients with interstitial lung disease diagnoses other than idiopathic pulmonary fibrosis (HR 0.73 [0.16-3.41]; p=0.69). The association between telomere length and survival in patients with idiopathic pulmonary fibrosis was independent of age, sex, forced vital capacity, or diffusing capacity of carbon monoxide, and was replicated in the two independent idiopathic pulmonary fibrosis replication cohorts (Chicago cohort, HR 0.11 [0.03-0.39], p=0.00066; San Francisco cohort, HR 0.25 [0.07-0.87], p=0.029). INTERPRETATION: Shorter leucocyte telomere lengths are associated with worse survival in idiopathic pulmonary fibrosis. Additional studies will be needed to establish clinically relevant thresholds for telomere length and how this biomarker might affect risk stratification of patients with idiopathic pulmonary fibrosis. FUNDING: US National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, Harroun Family Foundation, and Nina Ireland Lung Disease Program.

Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: a report of three cases.

Sepsis with multi organ dysfunction syndrome (MODS) is the most common cause of death in patients in noncoronary intensive care units. Currently, there are no specific treatments that reduce mortality in patients with sepsis and MODS. We report three patients who received therapeutic plasma exchange (TPE) for sepsis with MODS who completely recovered. The first patient, a 3-year-old male presented with Methicillin-resistant Staphylococcus aureus-associated respiratory, renal, coagulation, hepatic, and neurologic dysfunction. After 5 TPEs, the patient fully recovered. The second patient was a 36-year-old pregnant female who developed MODS at 22 weeks of gestation. She had developed respiratory, hepatic, renal, cardiovascular, neurologic, and coagulation dysfunction following pneumonia and concurrent urinary tract infection resulting in an intrauterine fetal demise. After 8 TPEs, the patient was discharged home with only mild residual hepatic dysfunction. The third patient, a 50-year-old female with a history of seizure disorder, was found unresponsive in over 100°F heat and diagnosed with Staphylococcus aureus-associated MODS. Her respiratory, coagulation, neurologic, renal, and hepatic systems were affected. The patient underwent 6 TPEs after which she had marked improvement. In conclusion, TPE may be an effective adjunct therapy in MODS by possibly removing toxic mediators and replacing deficient factors using donor plasma.

Predicting out of intensive care unit cardiopulmonary arrest or death using electronic medical record data.

BACKGROUND: Accurate, timely and automated identification of patients at high risk for severe clinical deterioration using readily available clinical information in the electronic medical record (EMR) could inform health systems to target scarce resources and save lives. METHODS: We identified 7,466 patients admitted to a large, public, urban academic hospital between May 2009 and March 2010. An automated clinical prediction model for out of intensive care unit (ICU) cardiopulmonary arrest and unexpected death was created in the derivation sample (50% randomly selected from total cohort) using multivariable logistic regression. The automated model was then validated in the remaining 50% from the total cohort (validation sample). The primary outcome was a composite of resuscitation events, and death (RED). RED included cardiopulmonary arrest, acute respiratory compromise and unexpected death. Predictors were measured using data from the previous 24 hours. Candidate variables included vital signs, laboratory data, physician orders, medications, floor assignment, and the Modified Early Warning Score (MEWS), among other treatment variables. RESULTS: RED rates were 1.2% of patient-days for the total cohort. Fourteen variables were independent predictors of RED and included age, oxygenation, diastolic blood pressure, arterial blood gas and laboratory values, emergent orders, and assignment to a high risk floor. The automated model had excellent discrimination (c-statistic=0.85) and calibration and was more sensitive (51.6% and 42.2%) and specific (94.3% and 91.3%) than the MEWS alone. The automated model predicted RED 15.9 hours before they occurred and earlier than Rapid Response Team (RRT) activation (5.7 hours prior to an event, p=0.003) CONCLUSION: An automated model harnessing EMR data offers great potential for identifying RED and was superior to both a prior risk model and the human judgment-driven RRT.

Thoracic Cavernous Lymphangioma Provoking Massive Chyloptysis: A Case Report.

Chyloptysis is a relatively rare embodiment of disease that encompasses a lengthy differential and provides many diagnostic and therapeutic challenges. Presented here is the case of a young woman with massive chyloptysis due to a thoracic cavernous lymphangioma arising in the peripartum period. The severity of her condition mandated the use of cardiopulmonary bypass to resect her lymphangioma. We believe that the extent of her symptoms, etiology of disease, and surgical management represent a unique scenario in the literature.

Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations.

BACKGROUND: Telomerase is an enzyme that catalyzes the addition of nucleotides on the ends of chromosomes. Rare loss of function mutations in the gene that encodes the protein component of telomerase (TERT) have been described in patients with idiopathic pulmonary fibrosis (IPF). Here we examine the telomere lengths and pulmonary fibrosis phenotype seen in multiple kindreds with heterozygous TERT mutations. METHODS AND FINDINGS: We have identified 134 individuals with heterozygous TERT mutations from 21 unrelated families. Available medical records, surgical lung biopsies and radiographs were evaluated retrospectively. Genomic DNA isolated from circulating leukocytes has been used to measure telomere lengths with a quantitative PCR assay. We find that telomere lengths of TERT mutation carriers decrease in an age-dependent manner and show progressive shortening with successive generations of mutation inheritance. Family members without TERT mutations have a shorter mean telomere length than normal, demonstrating epigenetic inheritance of shortened telomere lengths in the absence of an inherited TERT mutation. Pulmonary fibrosis is an age-dependent phenotype not seen in mutation carriers less than 40 years of age but found in 60% of men 60 years or older; its development is associated with environmental exposures including cigarette smoking. A radiographic CT pattern of usual interstitial pneumonia (UIP), which is consistent with a diagnosis of IPF, is seen in 74% of cases and a pathologic pattern of UIP is seen in 86% of surgical lung biopsies. Pulmonary fibrosis associated with TERT mutations is progressive and lethal with a mean survival of 3 years after diagnosis. Overall, TERT mutation carriers demonstrate reduced life expectancy, with a mean age of death of 58 and 67 years for males and females, respectively. CONCLUSIONS: A subset of pulmonary fibrosis, like dyskeratosis congenita, bone marrow failure, and liver disease, represents a "telomeropathy" caused by germline mutations in telomerase and characterized by short telomere lengths. Family members within kindreds who do not inherit the TERT mutation have shorter telomere lengths than controls, demonstrating epigenetic inheritance of a shortened parental telomere length set-point.

COPD: a dust-induced disease?

Various reports have demonstrated the importance of small airway inflammation in the development of airflow limitation and progression of COPD. This hypothesis proposes that the pathogenesis of COPD mirrors a chronic inhalational dust-induced disease. The putative inorganic dust in cigarette smoke is aluminum silicate or kaolinite, a common component of clay soils. Kaolinite has been recovered in the alveolar macrophages of smokers and has been reported as a constituent of tobacco products. The origin of kaolinite in tobacco products remains unknown, and possible potential sources are proposed. On inhalation, kaolinite deposition in the distal lung may promote macrophage accumulation within the terminal airways leading to a respiratory bronchiolitis. In the susceptible smoker, important genetic, environmental, immunologic, and mechanical factors interact and modulate this small airway inflammation, ultimately leading to the pathologic lesion of emphysema. Further studies into the effects of kaolinite on macrophage function and the subsequent development of respiratory bronchiolitis could lead to prevention of COPD at its precursor lesion.

Pulmonary prostacyclin synthase overexpression chemoprevents tobacco smoke lung carcinogenesis in mice.

Increased pulmonary production of prostaglandin I2 (prostacyclin) by lung-specific overexpression of prostacyclin synthase decreases lung tumor incidence and multiplicity in chemically induced murine lung cancer models. We hypothesized that pulmonary prostacyclin synthase overexpression would prevent lung carcinogenesis in tobacco-smoke exposed mice. Murine exposure to tobacco smoke is an established model of inducing pulmonary adenocarcinomas and allows for the testing of potential chemopreventive strategies. Transgenic FVB/N mice with lung-specific prostacyclin synthase overexpression were exposed to mainstream cigarette smoke for 22 weeks and then held unexposed for an additional 20 weeks. All of the exposed animals developed bronchiolitis analogous to the respiratory bronchiolitis seen in human smokers. The transgenic mice, when compared with smoke-exposed transgene negative littermates, had significant decreases in tumor incidence and multiplicity. Significantly fewer transgenics (6 of 15; 40%) developed tumors compared with the tumor incidence in wild-type littermates (16 of 19; 84%; Fisher's exact test, P = 0.012). Tumor multiplicity was also significantly decreased in the transgenic animals (tg+ = 0.4 +/- 0.5 versus wild-type = 1.2 +/- 0.86 tumors/mouse; P < 0.001). Targeted prostaglandin levels at the time of sacrifice revealed significantly elevated prostaglandin I2 levels in the transgenic animals, coupled with significantly decreased prostaglandin E2 levels. Gene expression analysis of isolated type II pneumocytes suggests potential explanations for the observed chemoprevention, with Western blot analysis confirming decreased expression of cytochrome p450 2e1. These studies extend our previous studies and demonstrate that manipulation of prostaglandin production distal to cyclooxygenase significantly reduces lung carcinogenesis in a tobacco smoke exposure model, and gene expression studies show critical alterations in antioxidation, immune response, and cytokine pathways.

Blue rubber bleb nevus syndrome: endobronchial involvement presenting as chronic cough.

This case report describes a rare presentation of chronic cough secondary to endobronchial involvement with blue rubber bleb nevus syndrome (BRBNS) lesions. BRNBS is a rare syndrome characterized with cavernous hemangiomas involving the skin and GI tract. We report the case of a 37-year-old woman, with known BRBNS, who acquired an intractable cough with a radiograph revealing multiple pulmonary nodules. A bronchoscopy demonstrated various bluish, raised, and hypervascular lesions characteristic for BRBNS involving the right mainstem bronchus and segmental bronchi. To our knowledge, this is the first report of endobronchial involvement with BRBNS.

Recuento histórico Escuela de Medicina de la Universidad de Puerto Rico 1950-2000 / Historical recollection Medical School of the University of Puerto Rico 1950-2000

The School of Medicine of the University of Puerto Rico was founded in 1950 with the mission of educating the much needed physician workforce in order to improve the health of a large portion of the population in Puerto Rico. The main events in its first fifty years of existence are summarized. Emphasis is given to the unique, mutually dependent association between the School of Medicine and the Department of Health of Puerto Rico. Soon after its organization, the school became a principal protagonist in the delivery of specialized medical care to the medically indigent population within the existing Regionalization Program of Health Care services in the island. With the creation and development of various other academic and health services institutions in the island, and the advent of a new system of health care in 1993, based on managed care; the School's interdependence with the Department of Health and its role in the direct care of the medically indigent have waned drastically. The School now faces its greatest challenges as it begins to insert itself into the economically competitive arena of the new health care system; and in redefining its commitments, while searching for new resources, alliances, teaching faculty, hospitals and clinics, enabling it to maintain its leadership in medical education, specialty training and scientific research in Puerto Rico.

Recuento histórico Escuela de Medicina de la Universidad de Puerto Rico 1950-2000 / Historical recollection Medical School of the University of Puerto Rico 1950-2000

The School of Medicine of the University of Puerto Rico was founded in 1950 with the mission of educating the much needed physician workforce in order to improve the health of a large portion of the population in Puerto Rico. The main events in its first fifty years of existence are summarized. Emphasis is given to the unique, mutually dependent association between the School of Medicine and the Department of Health of Puerto Rico. Soon after its organization, the school became a principal protagonist in the delivery of specialized medical care to the medically indigent population within the existing Regionalization Program of Health Care services in the island. With the creation and development of various other academic and health services institutions in the island, and the advent of a new system of health care in 1993, based on managed care; the School's interdependence with the Department of Health and its role in the direct care of the medically indigent have waned drastically. The School now faces its greatest challenges as it begins to insert itself into the economically competitive arena of the new health care system; and in redefining its commitments, while searching for new resources, alliances, teaching faculty, hospitals and clinics, enabling it to maintain its leadership in medical education, specialty training and scientific research in Puerto Rico.(AU)