A carbon monoxide 'single breath' method to measure total haemoglobin mass: a feasibility study.

NEW FINDINGS: What is the central question of this study? Is it possible to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in ventilated patients? What is the main finding and its importance? A 'single breath' of CO with a subsequent 30 s breath hold provides almost as exact a measure of haemoglobin mass as the established optimized CO-rebreathing method when applied to healthy subjects. The modified method has now to be checked in ventilated patients before it can be used to quantify the contributions of blood loss and of dilution to the severity of anaemia. ABSTRACT: Anaemia is defined by the concentration of haemoglobin (Hb). However, this value is dependent upon both the total circulating haemoglobin mass (tHb-mass) and the plasma volume (PV) - neither of which is routinely measured. Carbon monoxide (CO)-rebreathing methods have been successfully used to determine both PV and tHb-mass in various populations. However, these methods are not yet suitable for ventilated patients. This study aimed to modify the CO-rebreathing procedure such that a single inhalation of a CO bolus would enable its use in ventilated patients. Eleven healthy volunteers performed four CO-rebreathing tests in a randomized order, inhaling an identical CO volume. In two tests, CO was rebreathed for 2 min (optimized CO rebreathing; oCOR), and in the other two tests, a single inhalation of a CO bolus was conducted with a subsequent breath hold of 15 s (Procnew 15s) or 30 s (Procnew 30s). Subsequently, the CO volume in the exhaled air was continuously determined for 20 min. The amount of CO exhaled after 7 and 20 min was respectively 3.1 ± 0.3 and 5.9 ± 1.1 ml for oCOR, 8.7 ± 3.6 and 12.0 ± 4.4 ml for Procnew 15s and 5.1 ± 2.0 and 8.4 ±2.6 ml for Procnew 30s. tHb-mass was 843 ± 293 g determined by oCOR, 821 ± 288 g determined by Procnew 15s (difference: P < 0.05) and 849 ± 311 g determined by Procnew 30s. Bland-Altman plots demonstrated slightly lower tHb-mass values for Procnew 15s compared with oCOR (-21.8 ± 15.3 g) and similar values for Procnew 30s. In healthy volunteers, a single inhalation of a CO bolus, preferably followed by a 30 s breath hold, can be used to determine tHb-mass. These results must now be validated for ventilated patients.

Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery.

BACKGROUND: Intraoperative mortality is now rare, but death within 30 days of surgery remains surprisingly common. Perioperative myocardial infarction is associated with a remarkably high mortality. There are strong associations between hypotension and myocardial injury, myocardial infarction, renal injury, and death. Perioperative arterial blood pressure management was thus the basis of a Perioperative Quality Initiative consensus-building conference held in London in July 2017. METHODS: The meeting featured a modified Delphi process in which groups addressed various aspects of perioperative arterial pressure. RESULTS: Three consensus statements on intraoperative blood pressure were established. 1) Intraoperative mean arterial pressures below 60-70 mm Hg are associated with myocardial injury, acute kidney injury, and death. Injury is a function of hypotension severity and duration. 2) For adult non-cardiac surgical patients, there is insufficient evidence to recommend a general upper limit of arterial pressure at which therapy should be initiated, although pressures above 160 mm Hg have been associated with myocardial injury and infarction. 3) During cardiac surgery, intraoperative systolic arterial pressure above 140 mm Hg is associated with increased 30 day mortality. Injury is a function of arterial pressure severity and duration. CONCLUSIONS: There is increasing evidence that even brief durations of systolic arterial pressure <100 mm Hg and mean arterial pressure <60-70 mm Hg are harmful during non-cardiac surgery.

Genetically Compromising Phospholipid Metabolism Limits Candida albicans' Virulence.

Perturbing ergosterol synthesis has been previously shown to reduce the virulence of Candida albicans. We tested the hypothesis that further altering cell membrane composition by limiting phospholipid synthesis or remodeling will have the same effect. To model partial inhibition, C. albicans strains independently harboring heterozygous deletion of four genes that encode for enzymes that mediate phospholipid synthesis or modification were generated. Quantitative PCR determined that heterozygous deletion routinely caused a nearly 50% reduction in the respective gene's transcript abundance. Compensatory increased transcript abundance was only found with the deletion of LRO1, a homolog of phospholipid diacylglycerol acyltransferases. Virulence of the mutants was assayed in a Caenorhabditis elegans host model. Even modestly reduced expression of LRO1, phosphatidylserine synthase (CHO1), and lysophospholipid acyltransferase (LPT1) significantly reduced virulence by 23-38%. Reintroducing a second functional allele, respectively, to all three mutants restored virulence. Heterozygous deletion of SLC1, a homolog of 1-acylglycerol-3-phosphate O-acyltransferases, did not significantly reduce virulence. Electrospray ionization tandem mass spectrometry analysis of phospholipid composition followed by principal component analysis identified comprehensive changes in the LRO1 and CHO1 deletion heterozygotes. Strikingly (p < 0.001), univariate comparisons found that both deletion heterozygotes had 20% more phosphatidylinositol, 75% less lysophosphatidylcholine, and 35% less lysophosphatidylethanolamine compared to wild type. Heterozygous deletion of LPT1 also significantly increased phosphatidylinositol abundance. No growth phenotype, including filamentation, was affected by any mutation. Together, these data predict that even partial pharmacological inhibition of Lro1p, Cho1p, and Lpt1p will limit C. albicans virulence through altering phospholipid composition.

Hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia.

In practice, clinicians generally consider anemia (circulating hemoglobin concentration < 120 g.l-1 in non-pregnant females and < 130 g.l-1 in males) as due to impaired hemoglobin synthesis or increased erythrocyte loss or destruction. Rarely is a rise in plasma volume relative to circulating total hemoglobin mass considered as a cause. But does this matter? We explored this issue in patients, measuring hemoglobin concentration, total hemoglobin mass (optimized carbon monoxide rebreathing method) and thereby calculating plasma volume in healthy volunteers, surgical patients, and those with inflammatory bowel disease, chronic liver disease or heart failure. We studied 109 participants. Hemoglobin mass correlated well with its concentration in the healthy, surgical and inflammatory bowel disease groups (r=0.687-0.871, P<0.001). However, they were poorly related in liver disease (r=0.410, P=0.11) and heart failure patients (r=0.312, P=0.16). Here, hemoglobin mass explained little of the variance in its concentration (adjusted R2=0.109 and 0.052; P=0.11 and 0.16), whilst plasma volume did (R2 change 0.724 and 0.805 in heart and liver disease respectively, P<0.0001). Exemplar patients with identical (normal or raised) total hemoglobin masses were diagnosed as profoundly anemic (or not) depending on differences in plasma volume that had not been measured or even considered as a cause. The traditional inference that anemia generally reflects hemoglobin deficiency may be misleading, potentially resulting in inappropriate tests and therapeutic interventions to address 'hemoglobin deficiency' not 'plasma volume excess'. Measurement of total hemoglobin mass and plasma volume is now simple, cheap and safe, and its more routine use is advocated.

Type 2 diabetes in a rapidly urbanizing region of Ghana, West Africa: a qualitative study of dietary preferences, knowledge and practices.

BACKGROUND: Urban centers in Sub-Saharan Africa, such as Kumasi, Ghana, are especially impacted by the dual burden of infectious and non-communicable disease (NCD), including a rise in type 2 diabetes mellitus (T2DM) prevalence. To develop effective intervention programs, the World Health Organization recommends more research to better understand the relationship between food consumption and the escalation of non-communicable disease such as T2DM. This study provides qualitative information about current food knowledge, attitudes and practices among T2DM patients and their caregivers in the region of Kumasi, Ghana. METHODS: In this qualitative study, three focus groups discussions of 30 persons total and 10 individual interviews were used to assess food preferences, knowledge, attitudes and practices of patients with T2DM as well as caregivers responsible for food preparation. Participants included both urban and rural dwellers. Hospital-based health talks were observed, a dietician was interviewed, and educational documents were collected. Themes were identified and coded using Nvivo10 software. RESULTS: Findings suggest that messages regarding sweetened foods, fats, use of seasonings and meal timing are followed. However, confusion exists regarding the impact of fruits, food portioning, plantains and processed foods on health outcomes for diabetic patients. Results also revealed a problem-solving approach to increasing vegetable consumption, and a concern about unhealthy food preferences among younger generations. CONCLUSIONS: Education about the impact of commonly available carbohydrates on blood sugar should be emphasized; messaging on portion sizes and certain foods should be more consistent; the economic benefits of local vegetable consumption should be promoted; and a research-informed, T2DM prevention campaign should be developed specifically for younger generations.

Stage of change and other predictors of participant retention in a behavioral weight management program in primary care.

High attrition often limits the efficacy of weight management programs, particularly those that serve primary care patients. We investigated stage of change and other predictors of retention in a behavioral intervention program that enrolled adult obese patients at three primary care sites. The program included practice improvements and provider training, as well as individual lifestyle counseling and educational group classes for participants. We analyzed predictors of whether participants returned for counseling visits and whether they attended group classes. The 461 participants were mainly women (84%) and minorities (87%), and most of them were in the preparation stage for dietary and physical activity changes. A total of 134 (29%) participants returned for at least one follow-up visit with their counselor and 85 (18%) attended at least one class. Baseline stage of change was not significantly associated with either return visits or class attendance (p = .875 and .182, respectively). Men and participants with children in the household were less likely to return for subsequent counseling sessions (p = .012 and .027, respectively). Age and employment were associated with class attendance (p = .099 and .034, respectively). Focus groups with participants confirmed that reasons for dropout included physical limitations or health issues, family issues, stress, and lack of social support. We conclude that prescreening of patients for readiness to participate and attention to personal barriers related to family and work might improve program retention. More frequent contacts between visits and stronger provider engagement might also strengthen the intervention.

The use of international service learning initiatives for global health education: case studies from Rwanda and Mexico.

Global health education and health promotion have the potential to engage students, scholars, and practitioners in ways that go beyond the classroom teaching routine. This engagement in global communities, can range from reflection on continuing deep-seated questions about human rights and civic responsibility to the use of health education and promotion-related theoretical, intellectual, and practical skills. In the arena of global health education and promotion, these skills also range from leadership and advocacy to decision making, critical and creative thinking, teamwork, and problem solving. In recent times, there has been a growing interest in cross-cultural collaborations and educational initiatives to improve stakeholder's understanding of global health principles and practices, to enrich the experiences of health professionals, and to improve the lives of those who are disenfranchised and live across borders. In this article of Health Promotion Practice, we highlight two unique cases of cross-national collaborations and provide a glimpse of the various shapes and forms taken by cross-cultural educational initiatives for global health education and promotion. We summarize the history, philosophy, and current working practices relevant to these collaborations, keeping in view the global health domains, competencies, and activities. In addition, we also compare the key components and activities of these two case studies from Rwanda and Mexico, wherein communities in these two countries collaborated with academic institutions and health professionals in the United States.

Cardiac Arrest Bundle of cARE Trial (CABARET) survey of current UK neuroprotective CPR practice.

Despite low out of hospital cardiac arrest (OOHCA) survival rates within the UK, animal studies hint at improved cerebral blood flow via a bundled neuroprotective CPR approach. The CABARET study introduces three key devices: the Head Up Position (HUP), Active Compression/Decompression (ACD) CPR, and the Impedance Threshold Device (ITD). A survey involving 27 UK pre-hospital critical care services indicated none are using these interventions widely, either alone or bundled. The CABARET team is now initiating a pilot study to investigate the feasibility of this CPR bundle, aiming to fill the prevailing evidence void in resuscitation research.

Cardiopulmonary exercise testing before and after intravenous iron in preoperative patients: a prospective clinical study.

BACKGROUND: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. METHODS: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l-1 and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment. RESULTS: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l-1 (mean rise 6.4% or 7.3 g l-1, p = < 0.0001, 95% CI 4.5-10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p = < 0.0001, 95% CI 29.4-69.2). Oxygen consumption at anerobic threshold ([Formula: see text] O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg-1 min-1, p = 0.09, 95% CI - 0.13 - 1.3). Peak oxygen consumption ([Formula: see text] O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.-1 min-1, p = 0.02, 95% CI 0.2-1.8) and peak work rate increased from 93 [67-112] watts to 96 [68-122] watts (p = 0.02, 95% CI 1.3-10.8). CONCLUSION: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 033 46213.

Filling Gaps and Setting Boundaries: Examining Utilization of Health and Social services at JeffHOPE Student Run Clinics.

The objective of this study was to describe the frequency that healthcare and social support services offered by JeffHOPE, a student run clinic for people experiencing homelessness in Philadelphia, PA, were utilized by patients. This study also aimed to investigate where patients would seek medical care on a given day had they not been able to access JeffHOPE. This study was conducted via mixed methods consisting of retrospective chart review of patient encounter records and a patient survey conducted weekly throughout 2019, both at a single clinic site, and retrospective chart review of January through March 2020 records at 5 clinic sites. This study found that the frequency of services utilized varied between clinic sites, and that Pharmacy and Procedure committees were the most utilized when examining the combined clinic data. Additionally, the survey found that JeffHOPE provided medical care to those that otherwise would not have sought it. Clinics also served as an alternative to accessing care for non-emergent issues in an Emergency Department (ED) for some patients, but for others it replaced seeing their primary care provider (PCP). This study confirmed that the services offered by JeffHOPE are well-utilized by patients experiencing homelessness in Philadelphia. It also revealed that while the organization's medical services filled care gaps and potentially decreased unnecessary ED visits, they were also sometimes accessed in lieu of a PCP visit. A focused effort on linkage to formal primary care services for all JeffHOPE patients and expanding collection of more granular data to all clinics represent important future endeavors for this student run organization.

Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease.

BACKGROUND: Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. METHODS: Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing. RESULTS: The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. CONCLUSIONS: The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.

Visual Impairment and Ocular Pathology Among the Urban American Homeless.

INTRODUCTION: There are few studies that describe the prevalence of ocular morbidity among people who are homeless in the United States. The goal of this study was to describe rates of visual impairment and ocular pathology of men at a homeless shelter in a major United States city. METHODS: An ophthalmologist lead eye-screening clinic was established at a homeless shelter in Philadelphia, Pennsylvania. Results were obtained prospectively from 2015 to 2017. RESULTS: During the study period, 91 patients were enrolled. Visual impairment, defined as vision worse than 20/40, was identified in 42% and ocular pathology in 57% of those studied. This was higher than the national average and higher than or similar to international studies conducted in homeless shelters. Common findings included cataracts, glaucoma, and past eye trauma. CONCLUSION: This study describes a high rate of eye disease and refractive error in an urban homeless sample in the United States.

Modifiable cardiovascular risk factors among individuals in low socioeconomic communities and homeless shelters.

To understand cardiovascular health in low socioeconomic populations, we analyzed the data from 426 low socioeconomic community-dwelling males and females and 287 homeless males in Philadelphia. Despite higher prevalence of smoking and hypertension, the proportion of homeless participants at increased risk for coronary heart disease was comparable with that of low socioeconomic community-dwelling participants. Among various characteristics, emotional stress was significantly associated with coronary heart disease risk in low socioeconomic community-dwelling participants only, suggestive of a differential psychosocial effect of stress. Our findings suggest that low socioeconomic populations are heterogeneous with respect to their risk factors and needs for interventions.

Replicating measurements of total hemoglobin mass (tHb-mass) within a single day: precision of measurement; feasibility and safety of using oxygen to expedite carbon monoxide clearance.

Hemoglobin concentration ([Hb]) is a function of total hemoglobin mass (tHb-mass) and plasma volume. [Hb] may fall by dilution due to plasma volume expansion and changes in the perioperative period may therefore correlate poorly with blood loss. A simple, reliable, repeatable way to measure plasma volume and tHb-mass would have substantial clinical utility. The "optimized carbon monoxide re-breathing method" (oCOR) meets these criteria. However, it is recommended that a minimum of 12 h (when breathing room air) is left between repeat measurements. Twenty-four subjects underwent 3 days of testing. Two oCOR tests were performed (T1 and T2), 3 h apart, with a different CO clearance method employed between tests aiming to keep the carboxyhemoglobin level below 10%. The primary aim was to ascertain whether tHb-mass testing could be safely repeated within 3 h if carboxyhemoglobin levels were actively reduced by breathing supplemental oxygen (PROCA ). Secondary aims were to compare two other clearance methods; moderate exercise (PROCB ), or a combination of the two (PROCC ). Finally, the reliability of the oCOR method was assessed. Mean (SD) tHb-mass was 807.9 ± (189.7 g) (for T1 on day 1). PROCA lowered the carboxyhemoglobin level from the end of T1 (mean 6.64%) to the start of T2 (mean 2.95%) by a mean absolute value of 3.69%. For PROCB and PROCC the mean absolute decreases in carboxyhemoglobin were 4.00% and 4.31%, respectively. The fall in carboxyhemoglobin between T1 and T2 was greatest in PROCC ; this was statistically significantly lower than that of PROCA (P = 0.0039) and PROCB (P = 0.0289). The test-retest reliability for the measurement of total hemoglobin mass was good with a mean typical error (TE) of 2.0%. The oCOR method is safe and can be repeated within 3 h when carbon monoxide is suitably cleared between tests. Using oxygen therapy alone adequately achieves this.

Re-designing the pathway to surgery: better care and added value.

The case for radical pathway re-design before surgery is in part driven by healthcare system pressures which are in turn the result of continuously rising demand in the face of tightly constrained resources. Such circumstances tend to drive revolutionary, rather than incremental, change. The current approach to preoperative assessment, that typically occurs in the weeks leading up to surgery, but is all too often only a few days before surgery, results in a lost opportunity for perioperative physicians to improve patient care. Re-engineering this process based on a patient-focused, pathway-driven vision of perioperative medicine offers a means of exploiting this opportunity. This review explores drivers for change, the opportunity offered by pathway re-design, and suggests a variety of strategies to add value in the preoperative pathway, each of which is facilitated by early engagement between perioperative physician and patient: collaborative decision-making, collaborative behavioural change, targeted comorbidity management as well as expectation management and psychological preparation for surgery including surgery schools.

Health Literacy: Cancer Prevention Strategies for Early Adults.

Health literacy, the degree to which individuals have the capacity to obtain, process, and understand health information and services needed to make health decisions, is an essential element for early adults (aged 18-44 years) to make informed decisions about cancer. Low health literacy is one of the social determinants of health associated with cancer-related disparities. Over the past several years, a nonprofit organization, a university, and a cancer center in a major urban environment have developed and implemented health literacy programs within healthcare systems and in the community. Health system personnel received extensive health literacy training to reduce medical jargon and improve their patient education using plain language easy-to-understand written materials and teach-back, and also designed plain language written materials including visuals to provide more culturally and linguistically appropriate health education and enhance web-based information. Several sustainable health system policy changes occurred over time. At the community level, organizational assessments and peer leader training on health literacy have occurred to reduce communication barriers between consumers and providers. Some of these programs have been cancer specific, including consumer education in such areas as cervical cancer, skin cancer, and breast cancer that are targeted to early adults across the cancer spectrum from prevention to treatment to survivorship. An example of consumer-driven health education that was tested for health literacy using a comic book-style photonovel on breast cancer with an intergenerational family approach for Chinese Americans is provided. Key lessons learned from the health literacy initiatives and overall conclusions of the health literacy initiatives are also summarized.