Breaking Barriers: An Innovative Tool to Assess the National and City-Level Physical Activity Policy Development to Practice Disconnect.

BACKGROUND: Population-level physical activity increases are improbable without intersectoral collaboration across government levels and sectors to develop and implement physical activity promotion policies. This study aims to provide information about the development of the Interaction between National and Local Government Levels in Development and Implementation of Physical Activity Policies Tool (INTEGRATE PA-Pol). A framework was created to examine the development and implementation of national and subnational physical activity policies and the (mis)alignment between government levels. METHODS: The work was conducted in 3 phases: (1) a scoping review was carried out to identify local government physical activity promotion policies and instruments for assessing them, (2) an expert group designed 6 questionnaires, and (3) cognitive response testing was employed for validity testing and item modification with a panel of research and policy experts. RESULTS: The INTEGRATE PA-Pol Tool consists of 6 questionnaires assessing how national and subnational governments collaborate to develop and implement physical activity promotion policies. CONCLUSION: This tool can assist in better understanding the development and implementation of a public policy monitoring system that will allow for benchmarking and priority setting to comprehend how physical activity promotion policies are designed and executed.

In Vitro Model for Analysis of High-Flow Aerosol Delivery During Continuous Nebulization.

BACKGROUND: To understand the fate of aerosols delivered by high-flow nasal cannula using continuous nebulization, an open-source anatomical model was developed and validated with a modified real-time gamma ratemeter technique. Mass balance defined circuit losses. Responsiveness to infusion rate and device technology were tested. METHODS: A nasal airway cast derived from a computed tomography scan was converted to a 3-dimensional-printed head and face structure connected to a piston ventilator (breathing frequency 30 breaths/min, tidal volume 750 mL, duty cycle 0.50). For mass balance experiments, saline mixed with Technetium-99m was infused for 1 h. Aerosol delivery was measured using a gamma ratemeter oriented to an inhaled mass filter at the hypopharynx of the model. Background and dead-space effects were minimized. All components were imaged by scintigraphy. Continuous nebulization was tested at infusion rates of 10-40 mL/h with gas flow of 60 L/min using a breath-enhanced jet nebulizer (BEJN), and a vibrating mesh nebulizer. Drug delivery rates were defined by the slope of ratemeter counts/min (CPM/min) versus time (min). RESULTS: The major source of aerosol loss was at the nasal interface (∼25%). Significant differences in deposition on circuit components were seen between nebulizers. The nebulizer residual was higher for BEJN (P = .006), and circuit losses, including the humidifier, were higher for vibrating mesh nebulizer (P = .006). There were no differences in delivery to the filter and head model. For 60 L/min gas flow, as infusion pump flow was increased, the rate of aerosol delivery (CPM/min) increased, for BEJN from 338 to 8,111; for vibrating mesh nebulizer, maximum delivery was 2,828. CONCLUSIONS: The model defined sites of aerosol losses during continuous nebulization and provided a realistic in vitro system for testing aerosol delivery during continuous nebulization. Real-time analysis can quantify effects of multiple changes in variables (nebulizer technology, infusion rate, gas flow, and ventilation) during a given experiment.

Enhanced Aerosol Delivery During High-Flow Nasal Cannula Therapy.

BACKGROUND: Aerosolized drug delivery via high-flow nasal cannula (HFNC) decreases as gas flow is increased. To improve aerosol delivery, breath-enhanced jet nebulizer may increase aerosol output. This study tested that hypothesis and compared breath-enhanced jet nebulizer to vibrating mesh nebulizer technology. METHODS: First, in an isolated circuit, breath-enhanced jet nebulizer and vibrating mesh nebulizer aerosol outputs were measured during simulated HFNC by using infused saline solution at rates of 5-60 mL/h. Limits were defined when nebulizer filling was detected. The devices were then tested by using 99mTc/saline solution to measure maximum rates of aerosol production. After the output experiments, drug delivery was measured in vitro by using a model that consisted of an HFNC circuit interfaced to a realistic 3-dimensional printed head. The 99mTc/saline solution was infused at rates of 5 to 60 mL/h for the breath-enhanced jet nebulizer and 5 to 20 mL/h for the vibrating mesh nebulizer with HFNC gas flows of 10 to 60 L/min. Aerosol delivery to the trachea was measured by using a shielded ratemeter, which defined the rate of drug delivery (µg NaCl/min). RESULTS: With increasing gas flow, breath-enhanced jet nebulizer output increased to a maximum of 50 mL/h, the vibrating mesh nebulizer maximum was 12 mL/h. At HFNC gas flow of 60 L/min, breath-enhanced jet nebulizer delivered 3.16 to 316.8 µg NaCl/min, the vibrating mesh nebulizer delivered 23.5 to 61.7 µg NaCl/min. For infusion pump flows of 5 to 12 mL/h, the rate of drug delivery was independent of nebulizer type (P = .19) and dependent on infusion pump flow (P < .001) and gas flow (P < .001). CONCLUSIONS: Increasing gas flow increased breath-enhanced jet nebulizer output, which demonstrated the effects of breath enhancement. At 60 L/min, breath enhanced jet nebulizer delivered up to 5 times more aerosol compared with conventional vibrating mesh nebulizer technology. Breath-enhanced jet nebulizer delivered a wide range of dose rates at all high flows. In patients who are critically ill, breath-enhanced jet nebulizer technology may allow titration of bedside dosing based on clinical response by simple adjustment of the infusion rate.

Pain Medicine Education in the United States: Success, Threats, and Opportunities.

The year 2022 marked the 30th anniversary of the first Accreditation Council for Graduate Medical Education (ACGME) accreditation of pain medicine training programs. Before this, the education of pain medicine practitioners was through primarily an apprenticeship model. Since accreditation, pain medicine education has grown under the national leadership of pain medicine physicians and educational experts from the ACGME, exemplified by the release of Pain Milestones 2.0 in 2022. The rapid growth of knowledge in pain medicine, along with its multidisciplinary nature, poses challenges of fragmentation, standardization of curriculum, and adaptation to societal needs. However, these same challenges present opportunities for pain medicine educators to shape the future of the specialty.

Thomas Dent Mütter, M.D. (1811 to 1859): Exemplar of Expertise.

Thomas Dent Mütter, a Philadelphia plastic surgeon in the 1840s, boldly championed anesthesia when few physicians were convinced of its virtues. He was an early advocate of handwashing and hygienic wound care and helped pioneer the concept of postoperative recovery units. A leader in education, Mütter used a highly interactive style of teaching and restructured medical school classes to raise the caliber of clinical training. He supplemented his lectures with a myriad of specimens that he amassed over 24 yr. In 1863, this vast collection would serve as the basis for the Mütter Museum, which remains active today. Mütter exemplified expertise by tirelessly pursuing new knowledge and methods for the benefit of his patients and students.

The Bupivacaine Story: A Tribute to George A. Albright, MD (1931-2020).

In 1979, George A. Albright, MD (1931-2020) published a controversial editorial in Anesthesiology that raised the question of bupivacaine cardiotoxicity. In it, he presented several cases of rapid cardiovascular collapse after administration of the highly lipophilic local anesthetic and called for further investigation. Although the scientific community initially resisted Dr Albright's idea, his editorial would ultimately lead to several important advancements in anesthesiology. In 1983, the US Food and Drug Administration issued a black box warning that recommended against the use of 0.75% bupivacaine in obstetric anesthesia. This warning would remain in place until 1999. In addition, Dr Albright's article led to the following changes: laboratory research that proved the cardiotoxicity of bupivacaine; the development of safer, stereoselective agents like ropivacaine; and the acceptance of lipid emulsion as a treatment for local anesthetic toxicity. In this article, C. Philip Larson, Jr, MDCM, Editor-in-Chief of Anesthesiology at the time of publication of Albright's manuscript, provides a unique perspective on the bupivacaine story.

Origins of the International Anesthesia Research Society, Anesthesia & Analgesia, and the World Federation of Societies of Anaesthesiologists: Lasting Legacies of Francis McMechan, MD.

Francis McMechan, MD, founded the National Anesthesia Research Society (NARS), which was the precursor to the International Anesthesia Research Society (IARS) and the first physician anesthesia organization in the United States that was devoted to the research goals of the specialty. NARS initially sponsored Current Researches in Anesthesia and Analgesia, and IARS remains the main parent organization of the journal to this day. Dr McMechan originally hoped to coordinate the scientific efforts of NARS/IARS with the political activities of several other organizations he had founded to achieve his ultimate goal of building a powerful and well-connected anesthesia community across the nation, and eventually around the world. About a decade after his death, Dr McMechan's sweeping global vision would be fulfilled by the creation of the World Federation of Societies of Anesthesiologists (WFSA). Although Dr McMechan's political organizations would eventually lose ground to the newer American Society of Anesthetists (ASA), his scientific organization and his inspiring international interest-embodied by IARS, Anesthesia & Analgesia, and WFSA-continue to thrive today.

A Century of Technology in Anesthesia & Analgesia.

Technological innovation has been closely intertwined with the growth of modern anesthesiology as a medical and scientific discipline. Anesthesia & Analgesia, the longest-running physician anesthesiology journal in the world, has documented key technological developments in the specialty over the past 100 years. What began as a focus on the fundamental tools needed for effective anesthetic delivery has evolved over the century into an increasing emphasis on automation, portability, and machine intelligence to improve the quality, safety, and efficiency of patient care.

The Editors-in-Chief of Anesthesia & Analgesia Over 100 Years: Creating the Voice of the Global Anesthesiology Community.

The year 2022 marks the 100th anniversary of Anesthesia & Analgesia, the longest-running anesthesiology publication in the world. Founded in 1922 as Current Researches in Anesthesia & Analgesia by the visionary and charismatic Francis McMechan, MD, the journal served as a reliable mirror for the key scientific and political issues facing the nascent specialty of anesthesiology. Under the leadership of 6 subsequent Editors-in-Chief over the ensuing century-Howard Dittrick, MD; T. Harry Seldon, MD; Nicholas M. Greene, MD; Ronald D. Miller, MD; Steven L. Shafer, MD; and Jean-Francois Pittet, MD-Anesthesia & Analgesia has grown in size, circulation, and impact. Today, it remains a formidable voice in the global anesthesia community.

Persistent Clostridium difficile Colitis Mimicking A Fatal Case Of Strongyloides Hyperinfection Syndrome.

Strongyloidiasis, a disease caused by the helminth Strongyloides stercoralis, has been identified as a life-threatening parasitic infection among immunocompromised patients. In the most severe cases, which include hyperinfection syndrome and dissemination of larvae throughout multiple organ sites, there is typically a history of immunosuppression among the infected. Herein, we describe a fatal case of S. stercoralis hyperinfection in an immigrant from rural Ecuador presenting with diarrhea along with Clostridium difficile colitis after the use of a prolonged course of steroids. Despite the appropriate administration of ivermectin, living Strongyloides larvae were discovered in a tracheal lavage. The patient ultimately developed a multiorgan failure requiring life-supporting measures in the intensive care unit and later succumbed to his condition. This case of S. stercoralis hyperinfection emphasizes the importance of screening for this parasite in the appropriate clinical scenarios. The diagnosis of S. stercoralis can be made more accessible to practitioners through the use of methods such as the modified Baermann technique, agar-plate culture, and serologic antibody testing.

Ambition for Self and for Specialty: Emery A. Rovenstine and the Politics of Organized Anesthesia, 1937-1947.

The letters between Emery Andrew Rovenstine, MD (1895-1960), and Arthur Ernest Guedel, MD (1883-1956), are a window into the personalities and politics of the creation of American anesthesiology. The ambition of these men, both personal and professional, lay at the heart of their sacrifices and successes. Their correspondence unmasked common struggles and foibles, humanizing these giants of our field. Notably throughout the letters, Rovenstine, as the junior partner, wrestled with Guedel's advice to temper personal ambition for the collective good. Over time, their relationship matured, and the junior eclipsed the senior. Still, at various points in his career, Rovenstine was censured for self-promotion by leaders in anesthesiology and the general medical community. These moments brought to light issues of continued relevance today: inner tension between individual and group ambition, and professional friction between academic and political priorities in anesthesiology. In the end, it was an unapologetic blend of ambition for self and ambition for the specialty that allowed Emery Rovenstine to make his unique imprint on American anesthesiology.

Treatment of obstructive sleep apnea with CPAP improves chronic inflammation measured by neutrophil-to-lymphocyte ratio.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with chronic inflammation likely triggered by nocturnal, intermittent hypoxemia and increased adrenergic tone. The neutrophil-to-lymphocyte ratio (NLR) was recently described as a measure of subclinical systemic inflammation. Studies on the effect of continuous positive airway pressure (CPAP) therapy in OSA on subclinical inflammation measured by NLR are lacking. We hypothesize that NLR levels would improve as chronic inflammation diminishes in patients with OSA treated with CPAP. METHODS: We retrospectively reviewed patients in whom OSA was diagnosed and who were treated with CPAP therapy. Complete blood count (CBC) were obtained pretreatment and posttreatment for calculation of NLR, which was calculated by dividing the number of neutrophils by the number of lymphocytes. Patients with conditions known to affect NLR such as chronic infections, inflammatory diseases, active cardiovascular disease, and malignancies were excluded from the study. CPAP adherence downloads were obtained for all patients. RESULTS: Out of 184 patients in whom OSA was diagnosed and who were treated with CPAP, 109 met our study criteria, including baseline polysomnogram, baseline and posttreatment CBC, and available adherence download. We compared the NLR before and after treatment with CPAP. There was a significant difference in NLR before and after treatment with CPAP (P < .0001). There was also a significant difference in apnea-hypopnea index before and after treatment (P < .0001). We also assessed the relationship between CPAP adherence (percentage of days used for > 4 hours) and the change in NLR. NLR decreased significantly in both the adherent (CPAP use ≥ 70% of days; P = .014) and nonadherent groups (CPAP use < 70% of days; P = .0003). Finally, we noticed a significant direct correlation between CPAP adherence beyond 70% and the change in NLR (ΔNLR) (P = .046) in patients who had ≥ 70% adherence with CPAP, which was not observed in patients with < 70% adherence. CONCLUSIONS: The NLR may be a useful marker for monitoring improvement, as CPAP had a desirable effect on the chronic inflammation induced by OSA when measured by NLR in this study. Our results specifically suggest that the NLR values decrease significantly in patients using CPAP regardless of adherence, but with a more direct relationship in those who use it beyond 70% of days, at least 4 hours a day.

Targeting c-Src Reverses Accelerated GPX-1 mRNA Decay in Chronic Obstructive Pulmonary Disease Airway Epithelial Cells.

Enhanced expression of the cellular antioxidant glutathione peroxidase (GPX)-1 prevents cigarette smoke-induced lung inflammation and tissue destruction. Subjects with chronic obstructive pulmonary disease (COPD), however, have decreased airway GPX-1 levels, rendering them more susceptible to disease onset and progression. The mechanisms that downregulate GPX-1 in the airway epithelium in COPD remain unknown. To ascertain these factors, analyses were conducted using human airway epithelial cells isolated from healthy subjects and human subjects with COPD and lung tissue from control and cigarette smoke-exposed A/J mice. Tyrosine phosphorylation modifies GPX-1 expression and cigarette smoke activates the tyrosine kinase c-Src. Therefore, studies were conducted to evaluate the role of c-Src on GPX-1 levels in COPD. These studies identified accelerated GPX-1 mRNA decay in COPD airway epithelial cells. Targeting the tyrosine kinase c-Src with siRNA inhibited GPX-1 mRNA degradation and restored GPX-1 protein levels in human airway epithelial cells. In contrast, silencing the tyrosine kinase c-Abl, or the transcriptional activator Nrf2, had no effect on GPX-1 mRNA stability. The chemical inhibitors for c-Src (saracatinib and dasanitib) restored GPX-1 mRNA levels and GPX-1 activity in COPD airway cells in vitro. Similarly, saracatinib prevented the loss of lung Gpx-1 expression in response to chronic smoke exposure in vivo. Thus, this study establishes that the decreased GPX-1 expression that occurs in COPD lungs is at least partially due to accelerated mRNA decay. Furthermore, these findings show that targeting c-Src represents a potential therapeutic approach to augment GPX-1 responses and counter smoke-induced lung disease.

Assessment of interstitial lung disease among black rheumatoid arthritis patients.

BACKGROUND: Conflicting reports exist regarding the racial and the gender distribution of rheumatoid arthritis-related interstitial lung disease (RA-ILD). In a major population study of predominately Whites, RA-ILD was reported mainly among smoker middle-aged men. However, recent data suggest that the disease is that of elderly women. Our study aimed to assess the prevalence and identify the gender differences and clinical characteristics of RA-ILD in a predominantly Black population. METHODS: Cross-sectional analysis of data obtained from the records of 1142 patients with RA diagnosis by ICD codes of which 503 cases met the inclusion criteria for the study. Eighty-six patients had chronic respiratory symptoms of cough and dyspnea and were further assessed by our multidisciplinary group of investigators. Thirty-two subjects with an established diagnosis of rheumatoid arthritis met the diagnostic criteria for interstitial lung disease. RESULTS: Of the 32 patients with RA-ILD, mean age was 62.6 ± 2.2 (± SEM), 93.7% were females, and 89% Blacks with a BMI = 29.2 (Kg/m2). Usual interstitial pneumonia (UIP) was found in 24/32 (75%) of the cases. Seventy-two percent of the RA-ILD patient had seropositive RA. Smoking history was reported in 31.3% of the cohort, gastroesophageal reflux disease (GERD) in 32.3%, and cardiovascular disease (CVD) risk factors in 65.6%. CONCLUSION: Our study indicates RA-ILD among Blacks is predominantly a disease of elderly females with higher rates of GERD and CVD risk factors. Further studies are needed to identify the pathogenetic differences accounting for the gender distribution of RA-ILD among Black and White populations.Key Points• First study to assess ILD among predominantly Black RA patients.• The prevalence of RA-associated ILD was 6.36%, affecting mostly women in their sixth decade with seropositive disease.• COPD was the most common airway disease among non-RA-ILD Black population.• GERD was found in approximately one-third of patients with RA-associated ILD versus one-fifth of those RA patients without any lung disease.

CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies.

Mineral bone disease (MBD) is a common complication of chronic kidney disease (CKD) characterized by disruption of normal mineral homeostasis within the body. One or more of the following may occur: hypocalcemia, hyperphosphatemia, secondary hyperparathyroidism (SHPT), decreased vitamin D and vascular calcification (VC). The greater the decrease in renal function, the worse the progression of CKD-MBD. These abnormalities may lead to bone loss, osteoporosis and fractures. CKD-MBD is a major contributor to the high morbidity and mortality among patients with CKD. Another well-known complication of CKD is cardiovascular disease (CVD) caused by increased atherosclerosis and VC. CVD is the leading cause of morbidity and mortality in CKD patients. VC is linked to reduced arterial compliance that may lead to widened pulse pressure and impaired cardiovascular function. VC is a strong predicator of cardiovascular mortality among patients with CKD. Elevated phosphorus levels and increased calcium-phosphorus product promote VC. Controlling mineral disturbances such as hyperphosphatemia and SHPT is still considered among the current strategies for treatment of VC in CKD through restriction of calcium based phosphate binders in hyperphosphatemic patients across all severities of CKD along with dietary phosphate restriction and use of calciminetics. Additionally, Vitamin D insufficiency is common in CKD and dialysis patients. The causes are multifactorial and a serious consequence is SHPT. Vitamin D compounds remain the first-line therapy for prevention and treatment of SHPT in CKD. Vitamin D may also have atheroprotective effects on the arterial wall, but clinical studies do not show clear evidence of reduced cardiovascular mortality with vitamin D administration. This review discusses the issues surrounding CKD-MBD, cardiovascular disease and approaches to treatment.

William James, Nitrous Oxide, and the Anaesthetic Revelation.

William James greatly influenced the fields of psychology, philosophy, and religion during the late 19th and early 20th centuries. This was the era of Modernism, a time when many writers rejected the certainty of Enlightenment ideals. Positivism, which rose to prominence in the early 19th century, had emphasized physical phenomena, empirical evidence, and the scientific method. Darwin's On the Origin of Species (1859), with its theory of natural selection, provided an explanation for the evolution of species apart from a divine Creator. Within this context, William James served as a "mediator between scientific agnosticism and the religious view of the world." James' own experience inhaling nitrous oxide played an important role in shaping his views. For James, the use of nitrous oxide served a key role in elucidating some of his most central ideas: 1) the value of religion, and the emphasis on mysticism and revelation (as opposed to theology and doctrine) as religion's foundation; 2) the universe as pluralistic (as opposed to absolutist, constant, eternal), driven by chance, experience, and change.

An unusual case of small bowel obstruction in a child caused by ingestion of water-storing gel beads.

Foreign body ingestion occurs most commonly in the pediatric population. Small bowel obstruction is a rare complication that can occur, and surgical intervention is required. We present the first report of a case of an 18-month-old child with a jejunal obstruction caused by ingestion of water-storing gel beads used for botanical arrangements. The child presented with obstipation and nonbloody, nonbilious emesis. Symptoms resolved after a large bead 3 cm in diameter was retrieved via laparoscopic-assisted excision. This case suggests that water-storing gel beads are particularly dangerous foreign bodies and should be kept out of the reach of children.

DNA prime/protein boost immunization against HIV clade C: safety and immunogenicity in mice.

The induction of both cellular and humoral immunity is an important goal for vaccine development against HIV. As a step towards the development of an efficacious vaccine against HIV clade C, the world's most prevalent strain, a combination DNA prime/protein boost immunization strategy was tested. A DNA expression vector was prepared encoding a codon-optimized env gene derived from a pediatric HIV clade C isolate, 1084i. Mice were immunized with HIV1084i env-encoding DNA, then boosted with homologous 1084i gp160. HIV1084i Env-specific T-cell responses were induced with DNA vaccination alone, but the strongest cellular immune responses were seen after boosting with gp160. Immunization with gp160 alone induced high-titer antibodies but required two inoculations. In contrast, high-titer antibodies were seen after a single 1084i gp160 boost in DNA-primed animals. All animals given gp160 inoculations, whether DNA primed or not, developed neutralizing antibodies reactive with HIV1084i and a macaque-passaged simian/human immunodeficiency construct, SHIV-1084ip. The results demonstrate the utility of this DNA prime/protein boost approach to generate cellular immunity, as well as neutralizing antibodies, against HIV clade C env antigens.