Electric impedance tomography-guided PEEP titration reduces mechanical power in ARDS: a randomized crossover pilot trial.

BACKGROUND: In patients with acute respiratory distress syndrome undergoing mechanical ventilation, positive end-expiratory pressure (PEEP) can lead to recruitment or overdistension. Current strategies utilized for PEEP titration do not permit the distinction. Electric impedance tomography (EIT) detects and quantifies the presence of both collapse and overdistension. We investigated whether using EIT-guided PEEP titration leads to decreased mechanical power compared to high-PEEP/FiO2 tables. METHODS: A single-center, randomized crossover pilot trial comparing EIT-guided PEEP selection versus PEEP selection using the High-PEEP/FiO2 table in patients with moderate-severe acute respiratory distress syndrome. The primary outcome was the change in mechanical power after each PEEP selection strategy. Secondary outcomes included changes in the 4 × driving pressure + respiratory rate (4 ΔP, + RR index) index, driving pressure, plateau pressure, PaO2/FiO2 ratio, and static compliance. RESULTS: EIT was consistently associated with a decrease in mechanical power compared to PEEP/FiO2 tables (mean difference - 4.36 J/min, 95% CI - 6.7, - 1.95, p = 0.002) and led to lower values in the 4ΔP + RR index (- 11.42 J/min, 95% CI - 19.01, - 3.82, p = 0.007) mainly driven by a decrease in the elastic-dynamic power (- 1.61 J/min, - 2.99, - 0.22, p = 0.027). The elastic-static and resistive powers were unchanged. Similarly, EIT led to a statistically significant change in set PEEP (- 2 cmH2O, p = 0.046), driving pressure, (- 2.92 cmH2O, p = 0.003), peak pressure (- 6.25 cmH2O, p = 0.003), plateau pressure (- 4.53 cmH2O, p = 0.006), and static respiratory system compliance (+ 7.93 ml/cmH2O, p = 0.008). CONCLUSIONS: In patients with moderate-severe acute respiratory distress syndrome, EIT-guided PEEP titration reduces mechanical power mainly through a reduction in elastic-dynamic power. Trial registration This trial was prospectively registered on Clinicaltrials.gov (NCT03793842) on January 4th, 2019.

Becoming a nurse faculty leader: doing your homework to minimize risk taking.

Risk taking is an important aspect of academic leadership; yet, how does taking risks shape leadership development, and what are the practices of risk taking in nurse faculty leaders? This interpretative phenomenological study examines the meaning and experience of risk taking among formal and informal nurse faculty leaders. The theme of doing your homework is generated through in-depth hermeneutic analysis of 14 interview texts and 2 focus group narratives. The practice of doing one's homework is captured in weighing costs and benefits, learning the context, and cultivating relationships. This study develops an evidence base for incorporating ways of doing one's homework into leadership development activities at a time when there is a tremendous need for nurse leaders in academic settings. Examining the practices of doing one's homework to minimize risk as a part of leadership development provides a foundation for cultivating nurse leaders who, in turn, are able to support and build leadership capacity in others.

Can a virtual patient trainer teach student nurses how to save lives--teaching nursing students about pediatric respiratory diseases.

INTRODUCTION: Virtual environments offer a variety of benefits and may be a powerful medium with which to provide nursing education. The objective of this study was to compare the achievement of learning outcomes of undergraduate nursing students when a virtual patient trainer or a traditional lecture was used to teach pediatric respiratory content. METHODS: This was a randomized, controlled, posttest design. A virtual pediatric hospital unit was populated with four virtual pediatric patients having different respiratory diseases that were designed to meet the same learning objectives as a traditional lecture. The study began in Spring 2010 with 93 Senior I, baccalaureate nursing students. Students were randomized to receive either a traditional lecture or an experience with a virtual patient trainer. Students' knowledge acquisition was evaluated using multiple-choice questions, and knowledge application was measured as timeliness of care in two simulated clinical scenarios using high-fidelity mannequins and standardized patients. RESULTS: Ninety-three students participated in the study, of which 46 were in the experimental group that received content using the virtual patient trainer. After the intervention, students in the experimental group had significantly higher knowledge acquisition (P = 0.004) and better knowledge application (P = 0.001) for each of the two scenarios than students in the control group. CONCLUSIONS: The purpose of this project was to compare a virtual patient trainer to a traditional lecture for the achievement of learning outcomes for pediatric respiratory content. Although the virtual patient trainer experience produced statistically better outcomes, the differences may not be clinically significant. The results suggest that a virtual patient trainer may be an effective substitute for the achievement of learning outcomes that are typically met using a traditional lecture format. Further research is needed to understand how best to integrate a virtual patient trainer into undergraduate nursing education.

Becoming a nurse faculty leader: facing challenges through reflecting, persevering and relating in new ways.

AIM: The aim of the present study was to explore the experience of becoming a nurse faculty leader. BACKGROUND: In a recent interpretation of 23 interviews conducted with nurse faculty leaders from across the United States about their experiences of becoming a leader three themes were identified: being thrust into leadership, taking risks and facing challenges. EVALUATION: This interpretive phenomenological study further explicates three aspects of how nurse educators faced challenges in becoming and serving as a leader. KEY ISSUES: Facing challenges meant reflecting, persevering through difficulties and learning to relate to others in new ways. Exemplars of participant experiences are provided for concreteness, to assist readers in determining how findings resonate with their own experience and how they can actualize this resonance in their own leadership practice. CONCLUSIONS: In the present study, reflecting, persevering through difficulties and learning to relate with others in a new way was how leaders faced challenges. IMPLICATIONS FOR NURSING MANAGEMENT: Leadership development opportunities that facilitate self-exploration, caring and thoughtful interactions with others and values clarification serve as the foundation for becoming a nurse faculty leader who is, in turn, able to build leadership capacity in other individuals and organizations.

A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer.

PURPOSE: Several sustained-release morphine (SRM) formulations are available internationally. This study compared 2 such products available in the United States, SR1 and SR2. PATIENTS AND METHODS: In an open-label study, patients with advanced cancer pain were randomized to receive SR1 or SR2 every 12 hours around-the-clock (ATC) for 5 days, with immediate release (IR) liquid morphine for rescue dosing (RD). Efficacy, safety, and patient acceptability were determined. RESULTS: A total of 32 patients were evaluable for efficacy and toxicity. Pain scores, RD dosage, RD frequency over 5 days, RD within 3 hours before and after the scheduled SRM, and 8 of the 11 evaluated side effects were higher in the SR1 group. At presumed morphine steady state (day 3), pain scores (P = .05), RD dosage (P = .07), RD frequency (P = .07), and number of RD +/-3 hours from scheduled SRM dose (P = .05) were consistently greater in the SR1 group (despite a higher median morphine dose in that group). There was a clinically important and directionally consistent trend that favored SR2, although not all were statistically significant. Patient preference favored SR2 (P < .05). Neither group had difficulty swallowing SR1 or SR2. CONCLUSIONS: This is the first study that directly compared two 12-hour SRM formulations. The data suggested, by multiple clinically important measures, that SR2 may provide superior analgesic efficacy and less toxicity compared to SR1. It also supports the concept that it cannot be assumed that different SR formulations of a given opioid are clinically equivalent. A larger study is needed to confirm our findings.

Symptom evaluation in palliative medicine: patient report vs systematic assessment.

PURPOSE: This study examined symptoms reported by patients after open-ended questioning vs those systematically assessed using a 48-question survey. MATERIALS AND METHODS: Consecutive patients referred to the palliative medicine program at the Cleveland Clinic Foundation were screened. Open-ended questions were asked initially followed by a 48-item investigator-developed symptom checklist. Each symptom was rated for severity as mild, moderate, or severe. Symptom distress was also evaluated. Data were collected using standardized pre-printed forms. RESULTS: Two hundred and sixty-five patients were examined and 200 were eligible for assessment. Of those assessed, the median age was 65 years (range 17-90), and median ECOG performance status was 2 (range 1-4). A total of 2,397 symptoms were identified, 322 volunteered and 2,075 by systematic assessment. The median number of volunteered symptoms was one (range zero to six). Eighty-three percent of volunteered symptoms were moderate or severe and 17% mild. Ninety-one percent were distressing. Fatigue was the most common symptom identified by systematic assessment but pain was volunteered most often. The median number of symptoms found using systematic assessment was ten (0-25). Fifty-two percent were rated moderate or severe and 48% mild. Fifty-three percent were distressing. In total, 69% of 522 severe symptoms and 79% of 1,393 distressing symptoms were not volunteered. Certain symptoms were more likely to be volunteered; this was unaffected by age, gender, or race. CONCLUSION: The median number of symptoms found using systematic assessment was tenfold higher (p<0.001) than those volunteered. Specific detailed symptom inquiry is essential for optimal palliation in advanced disease.

YycH regulates the activity of the essential YycFG two-component system in Bacillus subtilis.

Of the numerous two-component signal transduction systems found in bacteria, only a very few have proven to be essential for cell viability. Among these is the YycF (response regulator)-YycG (histidine kinase) system, which is highly conserved in and specific to the low-G+C content gram-positive bacteria. Given the pathogenic nature of several members of this class of bacteria, the YycF-YycG system has been suggested as a prime antimicrobial target. In an attempt to identify genes involved in regulation of this two-component system, a transposon mutagenesis study was designed to identify suppressors of a temperature-sensitive YycF mutant in Bacillus subtilis. Suppressors could be identified, and the prime target was the yycH gene located adjacent to yycG and within the same operon. A lacZ reporter assay revealed that YycF-regulated gene expression was elevated in a yycH strain, whereas disruption of any of the three downstream genes within the operon, yycI, yycJ, and yycK, showed no such effect. The concentrations of both YycG and YycF, assayed immunologically, remained unchanged between the wild-type and the yycH strain as determined by immunoassay. Alkaline phosphatase fusion studies showed that YycH is located external to the cell membrane, suggesting that it acts in the regulation of the sensor domain of the YycG sensor histidine kinase. The yycH strain showed a characteristic cell wall defect consistent with the previously suggested notion that the YycF-YycG system is involved in regulating cell wall homeostasis and indicating that either up- or down-regulation of YycF activity affects this homeostatic mechanism.

The business of palliative medicine--Part 3: The development of a palliative medicine program in an academic medical center.

Palliative medicine is the total continuing care of patients with cancer. Most resources for cancer care focus on curative attempts while often ignoring the symptoms created by the disease and its treatment. Attempts at curative treatment of the malignancy must be coupled with pain and symptom relief psychosocial and spiritual care, and support for the patient and family extending from the time of diagnosis through the bereavement period. To accomplish this important goal, we must establish comprehensive palliative medicine programs in cancer centers throughout the world. These programs must include education, research, and patient care and must work through an interdisciplinary team. The Cleveland Clinic Foundation palliative medicine program (PMP) is composed of a primary inpatient service, consult service, outpatient clinic, hospice homecare, and cancer homecare services. In this article, we describe the structure and development of the program and suggest future avenues for growth.

A syllabus for fellowship education in palliative medicine.

Recent years have seen significant growth in palliative medicine training programs and positions. There are plans to pursue palliative medicine specialty status with the American Board of Medical Specialties and accreditation of fellowship programs with the American College of Graduate Medical Education. A work group of program directors, supported initially by the Cleveland Clinic and then by the American Board of Hospice and Palliative Medicine, has recently published standards for fellowship training. Despite this, fundamental questions remain about defining the field and delineating the knowledge and skills expected following completion of specialty training. In this article, we describe the first fellowship program in palliative medicine (PMP) in the United States, developed and supported by the Cleveland Clinic Foundation. The program has been implemented as part of the Harry R. Horvitz Center for Palliative Medicine, founded in 1987 as the first comprehensive integrated US program in this field. This training program, in existence since 1989, features a traditional rotational structure with an inpatient primary care service, inpatient consult services, and an outpatient consult/hospice service. This article outlines the syllabus developed for this fellowship, given what we believe to be the essential knowledge base for the field of palliative medicine.

Complicated bereavement: a national survey of potential risk factors.

We developed a Bereavement Risk Questionnaire to rate 19 possible factors for assessing complicated bereavement. A four-point scale was used (0 = no risk, 3 = significant risk). The questionnaire was mailed nationwide in the United States to 508 hospice bereavement coordinators, and 262 responded. Most rated the following as significant risks: perceived lack of caregiver social support (70 percent), caregiver history of drug/alcohol abuse (68 percent), caregiver poor coping skills (68 percent), caregiver history of mental illness (67 percent), and patient is a child (63 percent). Overall, 61 percent chose perceived lack of social support, and 47 percent chose poor coping skills, as one of the top three risk factors. There was no relationship between professional discipline and responses. We found a consensus among bereavement professionals regarding important indicators in assessing bereavement risk. We conclude that it is possible to assess bereavement risk in caregivers of seriously ill patients, prior to the death of the patient. This would allow palliative care teams to allocate resources and services to those at the greatest risk for complicated bereavement.

Established and potential therapeutic applications of cannabinoids in oncology.

Cannabis occurs naturally in the dried flowering or fruiting tops of the Cannabis sativa plant. Cannabis is most often consumed by smoking marihuana. Cannabinoids are the active compounds extracted from cannabis. Recently, there has been renewed interest in cannabinoids for medicinal purposes. The two proven indications for the use of the synthetic cannabinoid (dronabinol) are chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Other possible effects that may prove beneficial in the oncology population include analgesia, antitumor effect, mood elevation, muscle relaxation, and relief of insomnia. Two types of cannabinoid receptors, CB1 and CB2, have been detected. CB1 receptors are expressed mainly in the central and peripheral nervous system. CB2 receptors are found in certain nonneuronal tissues, particularly in the immune cells. Recent discovery of both the cannabinoid receptors and endocannabinoids has opened a new era in research on the pharmaceutical applications of cannabinoids. The use of cannabinoids should be continued in the areas indicated, and further studies are needed to evaluate other potential uses in clinical oncology.

Communication of a cancer diagnosis: patients' perceptions of when they were first told they had cancer.

Fifty consecutive cancer patients cared for by a palliative medicine program were interviewed concerning the initial communication of their diagnosis. The majority of patients were satisfied with the manner and the circumstances in which the information was imparted. A minority of women were significantly more unhappy than men about the manner in which they were told. Sophisticated techniques are available to help physicians impart bad news effectively and humanely.

The cancer anorexia-cachexia syndrome: a survey of the Prognostic Inflammatory and Nutritional Index (PINI) in advanced disease.

Other than weight loss, most traditional methods of nutritional assessment are not acceptable in advanced cancer patients because they are inaccurate, too expensive for routine use, or too difficult for a debilitated person to complete. The prognostic inflammatory and nutritional index (PINI) is a formula devised to evaluate nutritional status and prognosis in critically ill patients. It has been suggested that the PINI score can be used to follow most pathological conditions. It has been measured in several settings and has been found to be a reliable indicator of both nutritional status and prognosis in trauma, burn, infected, and cardiac patients. In this pilot study, we evaluated the PINI in 50 consecutive patients referred to a palliative care service. Compared to a value in normal, healthy people of <1, the mean score in this sample was 102 (SD = 142, 95% CI = 62-142). The mean protein values were: alpha-1-acid glycoprotein 1409 mg/l (SD = 556, 95% CI = 1251-1567); C-reactive protein (CRP) 106 mg/l (SD = 89, 95% CI = 81-131); albumin 24 g/l (SD = 7, 95% CI = 23-26); and prealbumin 147 mg/l (SD = 73, 95% CI = 126-168). There was no significant association between the PINI and corticosteroid use, weight loss over time, age, or sex. These data indicate that the PINI is highly abnormal in our population. The CRP may be the most important value.

Autonomic nervous system dysfunction in advanced cancer.

The autonomic nervous system (ANS) innervates every organ in the body and is largely involuntary. There have been reports of autonomic dysfunction in cancer patients, but most are case reports. There are suggestions that this abnormality may be common in advanced cancer. Inpatients and outpatients with advanced cancer were enrolled. Patients were excluded if they had a previous diagnosis of a disease associated with autonomic nervous system (ANS) abnormalities, or had taken or were taking drugs affecting the ANS. Autonomic function was evaluated using five bedside cardiovascular tests: (1) heart rate response to deep breathing, (2) heart rate response to standing, (3) heart rate response to the Valsalva maneuver, (4) blood pressure response to standing and (5) blood pressure response to static exercise. Each test result was scored according to a validated scale of 0,.5, or 1. The individual scores were added together and each patient received a dysfunction score: none ( = 0-1), mild ( = 1.5-2), moderate ( = 2.5-3) or severe ( = 3.5-5). Twenty-eight men and 22 women participated, median age was 64 years. The median ECOG performance status was 2. Lung and prostate cancer were the most common ( N = 9, 5). 245 tests were performed; 86 (35%) individual tests were normal or borderline. Composite dysfunction scores were calculated; all the participants had a score consistent with abnormality. The median number of symptoms was 6 (range 1-15). Twenty-eight rated at least one symptom as severe (median 2, range 0-5), but symptoms did not correlate with test abnormalities. The results reveal significant ANS dysfunction in advanced cancer. There are more invasive tests that may give more accurate descriptions of ANS abnormalities in this population. These tests may help define the lesion better than these simple bedside tests. Further research with sophisticated ANS testing is needed to clearly define this paraneoplastic syndrome.

The efficacy and side effects of continuous infusion intravenous morphine (CIVM) for pain and symptoms due to advanced cancer.

Morphine is the strong opioid of choice in the management of moderate-to-severe chronic cancer pain. The preferred route of administration is oral, in individually titrated doses, regularly scheduled around the clock We conducted a retrospective study of continuous intravenous morphine (CIVM) in a palliative medicine program in 107 consecutive patients. The results suggest CIVM is an effective, safe, and versatile method of morphine administration when used with a defined protocol. Efficacy was similar to that obtained by others with intravenous morphine sulfate and also for oral morphine. Safety was suggested by the low incidence of dose-limiting side effects, most of which responded to dose reduction. Particularly noteworthy was the flexibility of CIVM with dose reduction in 20 percent.

Gastrointestinal symptoms among inpatients with advanced cancer.

Nearly one-half of the most frequently reported and most distressing symptoms in patients with advanced cancer are gastrointestinal in nature. This prospective study was designed to assess the frequency of gastrointestinal symptoms among inpatients admitted to a palliative medicine program with advanced cancer. Twenty-nine men and 2l women, with a median age of 64 years (range, 35-84), were interviewed about 17 gastrointestinal symptoms. Age, gender, diagnosis, and medication use were also recorded The most common diagnoses were cancers of the lung (n = 14), breast (n = 6), and prostate (n = 4). Dry mouth (84 percent), weight loss (76 percent), early satiety (71 percent), taste change (60 percent), constipation (58 percent), anorexia (56 percent), bloating (50 percent), nausea (48 percent), abdominal pain (42 percent), and vomiting (34 percent) were the 10 most common gastrointestinal symptoms. Women had more gastrointestinal symptoms than men (median 8 vs. 6, p = 0.018), although this finding was not statistically significant (p = 0.11) after excluding gender-specific cancers. Women had more taste change and diarrhea than men after excluding gender-specific cancers (p = 0.036 and p = 0.046, respectively). Those with primary gastrointestinal cancers (n = 8) had more indigestion and hiccups than those with nongastrointestinal cancers (n = 39). There was no age difference in symptomatology. The drugs prescribed most commonly were opioids (n = 40), laxatives (n = 38), H2 blockers (n = 29), appetite stimulants (n = 29), and antiemetics (n = 29). Findings support that gastrointestinal symptoms are very common in hospitalized patients with advanced cancer and that the frequency and type of symptoms differ with gender and gastrointestinal vs. nongastrointestinal primary site.

Cancer and chemotherapy-related upper gastrointestinal symptoms: the role of abnormal gastric motor function and its evaluation in cancer patients.

Disorders of gastric emptying are being increasingly recognized as the basis for "functional" symptoms in the general population. Recent research suggests that abnormal gastric emptying may also be the cause of common gastrointestinal problems in those with cancer, and can be a complication both of the disease and of its treatment. These disorders are diagnosed by measuring the rate of gastric emptying and comparing it with the normal rate. There are numerous methods of measurement available, each with inherent advantages and disadvantages. Differences in method application and a lack of standardization limit the extent to which results from different institutions can be compared. Because of the limitations of existing methods, new technology is frequently being evaluated. Radionuclide measurement is the current method of choice.

A phase II study of hydrocodone for cough in advanced cancer.

PURPOSE: Cough is a common symptom in advanced cancer. The use of hydrocodone as an antitussive has not been studied previously in this setting. This study evaluates hydrocodone for cough in advanced cancer METHODS: The results presented are from a phase II study with dose titration. SETTING: Palliative medicine program in a tertiary referral center PATIENTS: 25 consecutive patients with cough from irreversible causes, on a stable opioid regimen for the prior 24 hours, and no previous or current use of hydrocodone for cough. INTERVENTION: 5 mg hydrocodone was administered twice daily. The dose was then titrated daily (maximum: 60 mg/24 h), if needed, until a > or = 50 percent improvement of the frequency of cough was achieved and then maintained for three consecutive days. MEASUREMENTS: Cough severity, frequency, complications, and hydrocodone side effects. RESULTS: 20 persons (10 women and 10 men) completed study evaluation. Median age was 63 years (range: 42-82). Nine patients had lung cancer and seven had lung or pleura metastases; 19 patients had at least 50 percent improvement of their cough frequency. The median best response was 70 percent improvement in the cough frequency (range: 50-90 percent). Median hydrocodone dose associated with the best response was 10 mg/day (range: 5-30 mg/day). Cough severity, frequency, associated symptoms and complications, and activities of daily living improved significantly. Side effects of hydrocodone (dry mouth, nausea, and drowsiness) were tolerable and rated as mild. CONCLUSIONS: Hydrocodone is effective and safe to treat cough in advanced cancer A starting dose of 10 mg per day in divided doses seems effective. Dose escalation may be required. Most improved within one day.

Symptoms and prognosis in advanced cancer.

As death from cancer approaches, the associated symptoms become more important. Not only do these symptoms impair quality of life and guide palliative management of the patient, but some also appear to have prognostic value in determining clinical course and survival. A comprehensive prospective analysis of symptoms in 1,000 patients on initial referral to the Palliative Medicine Program of the Cleveland Clinic was conducted. Data were evaluated to determine any relationship between demographic characteristics, symptoms and subsequent survival. Shorter survival after referral to the Palliative Medicine Program was associated with male gender, poor performance status, dysphagia and early satiety. Dysphagia and early satiety were independently associated with reduced survival. There was a gender difference in survival favoring women. The effects of dysphagia, early satiety and gender were equal and nearly of similar magnitude to performance status. Symptom and gender analysis should be included in all cancer treatment and symptom control studies.

A phase II study of low-dose megestrol acetate using twice-daily dosing for anorexia in nonhormonally dependent cancer.

Anorexia is a common problem in advanced cancer. Low-dose megestrol acetate, a semi-synthetic progesterone, given twice daily, is an effective appetite stimulant in advanced cancer patients. There was an excellent correlation between patient satisfaction and the primary response criteria (appetite improvement). Given cost, side-effect profile, ease of administration, and efficacy, 80 mg twice daily after meals is an appropriate starting dose of megestrol acetate for anorexia in advanced cancer. If this is not effective, considerable dose escalation is possible.