Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses to Reduce Nonbeneficial Intensive Care Unit Treatments: Protocol for a Multicenter Quality Improvement Study.

BackgroundInvasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters. For patients with advanced medical illnesses receiving aggressive ICU treatments, TLTs can promote effective dialogue, develop consensus in decision making, and set rational boundaries to treatments based on patients' goals of care.ObjectiveThe aim of this study will be to examine whether a multicomponent quality-improvement strategy that uses protocoled TLTs as the default ICU care-planning approach for critically ill patients with advanced medical illnesses will decrease duration and intensity of nonbeneficial ICU care without changing hospital mortality.MethodsThis study will be conducted in medical ICUs of three public teaching hospitals in Los Angeles County. In Aim 1, we will conduct focus groups and semistructured interviews with key stakeholders to identify facilitators and barriers to implementing TLTs among ICU patients with advanced medical illnesses. In Aim 2, we will train clinicians to use protocol-enhanced TLTs as the default communication and care-planning approach in patients with advanced medical illnesses who receive invasive ICU treatments. Eligible patients will be those who the treating ICU physicians consider to be at high risk for nonbeneficial treatments according to guidelines from the Society of Critical Care Medicine. ICU physicians will be trained to use the TLT protocol through a curriculum of didactic lectures, case discussions, and simulations utilizing actors as family members in role-playing scenarios. Family meetings will be scheduled by trained care managers. The improvement strategy will be implemented sequentially in the three participating hospitals, and outcomes will be evaluated using a before-and-after study design. Key process outcomes will include frequency, timing, and content of family meetings. The primary clinical outcome will be ICU length of stay. Secondary outcomes will include hospital length of stay, days receiving life-sustaining treatments (eg, mechanical ventilation, vasopressors, and renal replacement therapy), number of attempts at cardiopulmonary resuscitation, frequency of invasive ICU procedures, and disposition from hospitalization.ResultsThe study began in August 2017. The implementation of interventions and data collection were completed at two of the three hospitals. As of September 2019, the study was at the postintervention stage at the third hospital. We have completed focus groups with physicians at each medical center (N=29) and interviews of family members and surrogate decision makers (N=18). The study is expected to be completed in the first quarter of 2020, and results are expected to be available in mid-2020.ConclusionsThe successful completion of the aims in this proposal may identify a systematic approach to improve communication and shared decision making and to reduce nonbeneficial invasive treatments for ICU patients with advanced medical illnesses.International registered report identifier (irrid)DERR1-10.2196/16301

Pulmonary Kaposi Sarcoma without Mucocutaneous Involvement: The Role of Sequential Thallium and Gallium Scintigraphy.

Kaposi sarcoma (KS) is a vascular-related tumor that has been associated with human immunodeficiency virus (HIV). It commonly involves the skin and lymph nodes, and infrequently involves the lungs. In very rare instances, pulmonary KS can be found in the absence of endobronchial and mucocutaneous involvement. Utilization of sequential thallium and gallium scintigraphy can aid in the diagnosis of pulmonary KS in the absence of mucocutaneous and endobronchial involvement. In this report, we discuss a case of a patient with acquired immunodeficiency syndrome who presented with dyspnea and cough and was found to have subtle pulmonary parenchymal nodular airspace opacities. He underwent negative infectious evaluation, including bronchoscopy. Despite the absence of mucocutaneous findings, sequential positive thallium and negative gallium scintigraphy led to an early diagnosis of pulmonary KS. Pulmonary KS in the absence of mucocutaneous involvement is a rare finding that is exceedingly difficult to diagnose. However, pulmonary KS should be considered in patients with HIV who present with respiratory symptoms even if the typical mucocutaneous manifestations of KS are absent. In such circumstances, sequential thallium and gallium scintigraphy can help differentiate pulmonary KS from other processes such as infections and lymphoma, and assist in establishing an earlier diagnosis

Oocyte maturation in the toad Rhinella arenarum (Amphibia, Anura): Evidence of cAMP involvement in steroid production and action

In this work, we describe the participation of the adenylate cyclase/3′-5′-cyclic adenonsine monophosphate (cAMP) pathway in the seasonal follicular secretion of progesterone (P 4 ) and testosterone (T), and its relationship with the maturation of Rhinella arenarum oocytes. Under gonadotropin stimulation, P 4 secretion was the dominant steroid produced during the reproductive period, resulting in 100% germinal vesicle breakdown (GVBD) in oocytes in vitro; in contrast, T and estradiol (E 2 ) secretion increased (∼16 nM/20 follicles and ∼80 pM/20 follicles, respectively) during the non-reproductive period, but only yielded 50% GVBD. Treatment of the follicles with dibutyryl-cAMP or forskolin induced a significant increase in T secretion during both periods, but P 4 secretion did not significantly change and GVBD did not occur. These results suggest that high cAMP levels in the oocyte maintain meiotic arrest and prevent the induction effect of follicular steroids. An increase in cAMP levels in denuded oocytes, however, negatively regulated T-induced maturation since treatment with increasing db-cAMP or forskolin inhibited their maturation. Therefore, we hypothesize that an elevation in T during the non-reproductive period favors its aromatization to E 2 , leading to follicle growth. During the reproductive period, P 4 production might promote oocyte maturation when environmental conditions are favorable for reproduction. Together, the results indicate that steroidogenesis is seasonal and depends on gonadotropic activity in R. arenarum.Fil: Arias Torres, Ana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Chilecito; ArgentinaFil: Páez, José B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Zelarayán, Liliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentin

Severe Cases of Pandemic H1N1 Pneumonia and Respiratory Failure Requiring Intensive Care

BackgroundThe objective of our study is to analyze the clinical data of patients with pandemic H1N1 2009 infection admitted to the intensive care unit (ICU) and to report key features observed among these patients.MethodsA total of 18 patients were admitted to our ICU between July and November 2009, with a primary diagnosis of influenza. Clinical data were analyzed to identify potential risk factors and characteristics thought to affect outcomes.ResultsOur patients were between ages 23 and 62 (mean 41). In all, 10 were obese. Two had no other comorbid conditions and 6 had obesity as their only comorbid condition. The most common symptoms were fever, shortness of breath, and cough. Laboratory data were notable for elevated creatine kinase levels, transaminitis, and lack of leukocytosis. The rapid influenza detection test (RIDT) had a 76% false negative result. Patients with a negative RIDT had their infection confirmed with real-time reverse transcriptase polymerase chain reaction (rRT-PCR). A total of 12 patients required invasive mechanical ventilation, with over half of whom responded only to nonconventional modes of ventilation. Most patients received high-dose (150 mg twice daily) oseltamivir. In all, 3 patients died and 11 were discharged without any long-term sequalae.ConclusionsUnlike seasonal influenza, our patients were not in the extremes of age. Most were obese and presented with severe respiratory distress and hypoxia in the summer months. A negative RIDT did not exclude pandemic H1N1 2009. Using a higher dose of oseltamivir and nonconventional modes of ventilation may have improved the outcome in our subset of patients. Hence, patients with a high clinical suspicion of severe influenza infection should be treated early and aggressively, even before confirmatory results are available

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe