Dignity Health

BACKGROUND: The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. METHODS: Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. RESULTS: In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. CONCLUSIONS: Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n = 55 and n = 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the "metasignature" for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers.

BACKGROUND: Since the introduction of mobile phones, technology has been increasingly used to enable diabetes self-management education and support. This timely systematic review summarizes how currently available technology impacts outcomes for people living with diabetes. METHODS: A systematic review of high quality review articles and meta analyses focused on utilizing technology in diabetes self-management education and support services was conducted. Articles were included if published between January 2013 and January 2017. RESULTS: Twenty-five studies were included for analysis. The majority evaluated the use of mobile phones and secure messaging. Most studies described healthy eating, being active and metabolic monitoring as the predominant self-care behaviors evaluated. Eighteen of 25 reviews reported significant reduction in A1c as an outcome measure. Four key elements emerged as essential for improved A1c: (1) communication, (2) patient-generated health data, (3) education, and (4) feedback. CONCLUSION: Technology-enabled diabetes self-management solutions significantly improve A1c. The most effective interventions incorporated all the components of a technology-enabled self-management feedback loop that connected people with diabetes and their health care team using 2-way communication, analyzed patient-generated health data, tailored education, and individualized feedback. The evidence from this systematic review indicates that organizations, policy makers and payers should consider integrating these solutions in the design of diabetes self-management education and support services for population health and value-based care models. With the widespread adoption of mobile phones, digital health solutions that incorporate evidence-based, behaviorally designed interventions can improve the reach and access to diabetes self-management education and ongoing support.

BACKGROUND: The epidemiology of osteomyelitis in the United States is largely unknown. The purpose of this study was to determine long-term secular trends in the incidence of osteomyelitis in a population-based setting. METHODS: The study population comprised 760 incident cases of osteomyelitis first diagnosed between January 1, 1969, and December 31, 2009, among residents of Olmsted County, Minnesota. The complete medical records for each potential subject were reviewed to confirm the osteomyelitis diagnosis and to extract details on anatomical sites, infecting organisms, etiological risk factors, and outcomes. RESULTS: The overall age and sex-adjusted annual incidence of osteomyelitis was 21.8 cases per 100,000 person-years. The annual incidence was higher for men than for women and increased with age (p < 0.001). Rates increased with the calendar year (p < 0.001) from 11.4 cases per 100,000 person-years in the period from 1969 to 1979 to 24.4 per 100,000 person-years in the period from 2000 to 2009. The incidence remained relatively stable among children and young adults but almost tripled among individuals older than sixty years; this was partly driven by a significant increase in diabetes-related osteomyelitis from 2.3 cases per 100,000 person-years in the period from 1969 to 1979 to 7.6 cases per 100,000 person-years in the period from 2000 to 2009 (p < 0.001). Forty-four percent of cases involved Staphylococcus aureus infections. CONCLUSIONS: The reasons for the increase in osteomyelitis between 1969 and 2009 are unclear but could comprise a variety of factors, including changes in diagnosing patterns or increases in the prevalence of risk factors (e.g., diabetes) in this population.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. Most GISTs present asymptomatically. They are best identified by computed tomography (CT) scan and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1. There have been many risk stratification classifications systems which are calculated based on tumor size, mitotic rate, location, and perforation. The approaches to treating GISTs are to resect primary low-risk tumors, resect high-risk primary or metastatic tumors with imatinib 400 mg daily for 12 months, or if the tumor is unresectable, neoadjuvant imatinib 400 mg daily followed by surgical resection is recommended. Sunitinib is required for KIT exon 9, 13, and 14 mutations, while ponatinib is used for exon 17 mutations and regorafenib for highly refractory tumors. High-risk tumors should be monitored for recurrence with serial abdominal CT scans. Radiofrequency ablation has shown to be effective when surgery is not suitable. Newer therapies of ipilimumab, nivolumab, and endoscopic ultrasound alcohol ablation have shown promising results. This report addresses the epidemiology, clinical presentation, diagnostic imaging, histologic diagnosis, classification and risk stratification, staging and grading, surgical treatment, adjuvant treatment, and metastasis of GISTs.

BACKGROUND: Dysbiotic vaginal microbiota have been implicated as contributors to persistent HPV-mediated cervical carcinogenesis and genital inflammation with mechanisms unknown. Given that cancer is a metabolic disease, metabolic profiling of the cervicovaginal microenvironment has the potential to reveal the functional interplay between the host and microbes in HPV persistence and progression to cancer. METHODS: Our study design included HPV-negative/positive controls, women with low-grade and high-grade cervical dysplasia, or cervical cancer (n = 78). Metabolic fingerprints were profiled using liquid chromatography-mass spectrometry. Vaginal microbiota and genital inflammation were analysed using 16S rRNA gene sequencing and immunoassays, respectively. We used an integrative bioinformatic pipeline to reveal host and microbe contributions to the metabolome and to comprehensively assess the link between HPV, microbiota, inflammation and cervical disease. FINDINGS: Metabolic analysis yielded 475 metabolites with known identities. Unique metabolic fingerprints discriminated patient groups from healthy controls. Three-hydroxybutyrate, eicosenoate, and oleate/vaccenate discriminated (with excellent capacity) between cancer patients versus the healthy participants. Sphingolipids, plasmalogens, and linoleate positively correlated with genital inflammation. Non-Lactobacillus dominant communities, particularly in high-grade dysplasia, perturbed amino acid and nucleotide metabolisms. Adenosine and cytosine correlated positively with Lactobacillus abundance and negatively with genital inflammation. Glycochenodeoxycholate and carnitine metabolisms connected non-Lactobacillus dominance to genital inflammation. INTERPRETATION: Cervicovaginal metabolic profiles were driven by cancer followed by genital inflammation, HPV infection, and vaginal microbiota. This study provides evidence for metabolite-driven complex host-microbe interactions as hallmarks of cervical cancer with future translational potential. FUND: Flinn Foundation (#1974), Banner Foundation Obstetrics/Gynecology, and NIH NCI (P30-CA023074).

This study evaluated the safety and feasibility of transendocardial injections of VentriGel, a cardiac extracellular matrix hydrogel, in early and late post-myocardial infarction (MI) patients with left ventricular (LV) dysfunction. VentriGel was delivered in 15 patients with moderate LV dysfunction (25% ≤ LV ejection fraction ≤ 45%) who were between 60 days to 3 years post-MI and were revascularized by percutaneous coronary intervention. The primary endpoints were incidence of adverse events and abnormal clinical laboratory results. This first-in-man study established the safety and feasibility of delivering VentriGel in post-MI patients, thus warranting further evaluation in larger, randomized clinical trials.

While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36γ was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.

OBJECTIVE: To assess the association between diet quality and intake of specific foods with disability and symptom severity in people with multiple sclerosis (MS). METHODS: In 2015, participants in the North American Research Committee on MS (NARCOMS) Registry completed a dietary screener questionnaire that estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red/processed meats. We constructed an overall diet quality score for each individual based on these food groups; higher scores denoted a healthier diet. We assessed the association between diet quality and disability status as measured using Patient-Determined Disease Steps (PDDS) and symptom severity using proportional odds models, adjusting for age, sex, income, body mass index, smoking status, and disease duration. We assessed whether a composite healthy lifestyle measure, a healthier diet, healthy weight (body mass index <25), routine physical activity, and abstinence from smoking was associated with symptom severity. RESULTS: Of the 7,639 (68%) responders, 6,989 reported physician-diagnosed MS and provided dietary information. Participants with diet quality scores in the highest quintile had lower levels of disability (PDDS; proportional odds ratio [OR] for Q5 vs Q1 0.80; 95% confidence interval [CI] 0.69-0.93) and lower depression scores (proportional OR for Q5 vs Q1 0.82; 95% CI 0.70-0.97). Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue (0.69; 95% CI 0.59-0.81), depression (0.53; 95% CI 0.43-0.66), pain (0.56; 95% CI 0.48-0.67), or cognitive impairment (0.67; 95% CI 0.55-0.79). CONCLUSIONS: Our large cross-sectional survey suggests a healthy diet and a composite healthy lifestyle are associated with lesser disability and symptom burden in MS.

This paper examines the transformation of local uncertainties encountered by working scientists into global certainty, or `scientific facts'. It discusses six mechanisms by which scientists transform local uncertainty: attributing certainty to the results of other fields; substituting processual for production evaluations in the face of technical failures; ideal type substitutions; shifting clinical and basic evaluation criteria; ad hoc generalizing of case studies; and the subsuming of epistemological questions in internal debates. The data are drawn from a study of late nineteenth-century British neurophysiologists (surgeons, neurologists, pathologists, physiologists). The approach is drawn from the sociology of work.

Aducanumab (Aduhelm) is approved in the United States for the treatment of patients with mild cognitive impairment due to Alzheimer's disease or mild AD dementia. Aducanumab Appropriate Use Recommendations (AURs) have been published and have helped guide best practices for use of aducanumab. As real-world use has occurred and more information has accrued, the AURs require refinement. We update the AURs to better inform appropriate patient selection and improve shared decision-making, safety monitoring, and risk mitigation in treated patients. Based on evolving experience we emphasize the importance of detecting past medical conditions that may predispose to amyloid related imaging abnormalities (ARIA) or may increase the likelihood of ARIA complications including autoimmune or inflammatory conditions, seizures, or disorders associated with extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype is strongly associated with ARIA and exhibits a gene dose effect. We recommend that clinicians perform APOE genotyping to better inform patient care decisions, discussions regarding risk, and clinician vigilance concerning ARIA. As most ARIA occurs during the titration period of aducanumab, we suggest performing MRI before the 5th, 7th, 9th, and 12th infusions to improve detection. Uncommonly, ARIA may be recurrent or serious; we suggest additional parameters for treatment discontinuation taking these observations into account. It is important to continue to learn from the real-world use of aducanumab and the AURs will continue to evolve as new information becomes available. This AUR update does not address efficacy, price, or insurance coverage and is provided to assist clinicians to establish best practices for use of aducanumab in the treatment of patients with mild cognitive impairment and mild Alzheimer's dementia.

By the most recent estimates, 34.2 million people in the U.S. have diabetes (1). At the same time, 88 million people are at increased risk for developing type 2 diabetes. The U.S. also sees an increasing prevalence of both type 1 and type 2 diabetes in children and adolescents (2). Thus, more than 122 million Americans are at risk for developing devastating complications associated with chronic hyperglycemia (1). Diabetes self-management education and support (DSMES) is a critical element of care for all people with diabetes (PWD). "The purpose of DSMES is to give PWD the knowledge, skills, and confidence to accept responsibility for their self-management. This includes collaborating with their healthcare team, making informed decisions, solving problems, developing personal goals and action plans, and coping with emotions and life stresses" (3). DSMES interventions include activities that support PWD to implement and sustain the self-management behaviors and strategies to improve diabetes and related cardiometabolic conditions and quality of life on an ongoing basis. Despite progress in diabetes treatment modalities, glycemic and cardiometabolic outcomes continue to decline in the U.S. (4). Now, more than ever, the provision of DSMES is a vital component of the full treatment for diabetes.

An underlying premise of the Affordable Care Act provisions that encourage employers to adopt health promotion programs is an association between workers' modifiable health risks and increased health care costs. Employers, consultants, and vendors have cited risk-cost estimates developed in the 1990s and wondered whether they still hold true. Examining ten of these common health risk factors in a working population, we found that similar relationships between such risks and total medical costs documented in a widely cited study published in 1998 still hold. Based on our sample of 92,486 employees at seven organizations over an average of three years, $82,072,456, or 22.4 percent, of the $366,373,301 spent annually by the seven employers and their employees in the study was attributed to the ten risk factors studied. This amount was similar to almost a quarter of spending linked to risk factors (24.9 percent) in the 1998 study. High risk for depression remained most strongly associated with increased per capita annual medical spending (48 percent, or $2,184, higher). High blood glucose, high blood pressure, and obesity were strongly related to increased health care costs (31.8 percent, 31.6 percent, and 27.4 percent higher, respectively), as were tobacco use, physical inactivity, and high stress. These findings indicate ongoing opportunities for well-designed and properly targeted employer-sponsored health promotion programs to produce substantial savings.

Department of Neurology, Box 0114, Vniversity of California, Sun Francisco, CA 94143 USA ∗Corresponding author: Howard L. Fields, M.D., Ph.D., Department of Neurology (M-794), University of California, San Francisco, CA 94143-0114, USA. Tel.: (415) 476-4201; FAX: (415) 476-9386. 1Present address: Department of Neuro-oncology and Pain Clinic, Dr. Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Submitted July 27, 1993; revised November 5, 1993; accepted November 8, 1993.

PURPOSE: The National Standards for Diabetes Self-Management Education and Support (DSMES) provide guidance and evidence-based, quality practice for all DSMES services. Due to the dynamic nature of health care and diabetes research, the National Standards are reviewed and revised approximately every 5 years by key stakeholders and experts within the diabetes care and education community. For each revision, the Task Force is charged with reviewing the current National Standards for appropriateness, relevance, and scientific basis and making updates based on current evidence and expert consensus. In 2021, the group was tasked with reducing administrative burden related to DSMES implementation across diverse care settings. CONCLUSION: The evidence supporting the 2022 National Standards clearly identifies the need to provide person-centered services that embrace cultural differences, social determinants of health, and the ever-increasing technological engagement platforms and systems. Payers are invited to review the National Standards as a tool to inform and modernize DSMES reimbursement requirements and to align with the evolving needs of people with diabetes (PWD) and physicians/other qualified health care professionals. The American Diabetes Association and the Association of Diabetes Care & Education Specialists strongly advocate for health equity to ensure all PWD have access to this critical service proven to improve outcomes both related to and beyond diabetes. The 2022 National Standards update is meant to be a universal document that is easy to understand and can be implemented by the entire health care community. DSMES teams in collaboration with primary care have been shown to be the most effective approach to overcome therapeutic inertia.

OBJECTIVE: To examine the effectiveness of the health system response to the challenge of diabetes across different settings and explore the inequalities in diabetes care that are attributable to socioeconomic factors. METHODS: We used nationally representative health examination surveys from Colombia, England, the Islamic Republic of Iran, Mexico, Scotland, Thailand and the United States of America to obtain data on diagnosis, treatment and control of hyperglycaemia, arterial hypertension and hypercholesterolaemia among individuals with diabetes. Using logistic regression, we explored the socioeconomic determinants of diagnosis and effective case management. FINDINGS: A substantial proportion of individuals with diabetes remain undiagnosed and untreated, both in developed and developing countries. The figures range from 24% of the women in Scotland and the USA to 62% of the men in Thailand. The proportion of individuals with diabetes reaching treatment targets for blood glucose, arterial blood pressure and serum cholesterol was very low, ranging from 1% of male patients in Mexico to about 12% in the United States. Income and education were not found to be significantly related to the rates of diagnosis and treatment anywhere except in Thailand, but in the three countries with available data insurance status was a strong predictor of diagnosis and effective management, especially in the United States. CONCLUSION: There are many missed opportunities to reduce the burden of diabetes through improved control of blood glucose levels and improved diagnosis and treatment of arterial hypertension and hypercholesterolaemia. While no large socioeconomic inequalities were noted in the management of individuals with diabetes, financial access to care was a strong predictor of diagnosis and management.

BACKGROUND: Limited data exist on procedural and biophysical indicators of pulmonary vein (PV) isolation durability after the cryoballoon ablation of atrial fibrillation (AF). OBJECTIVE: The aim of this study was to investigate the procedural and biophysical characteristics associated with late PV reconnection (PVR) and durable PV isolation (PVI) after cryoablation using the currently available second-generation cryoballoon. METHODS: Data from 435 PVs targeted in 112 consecutive patients who underwent a repeat procedure 14 ± 3 months after an index cryoablation of AF were examined. RESULTS: Altogether, 111 PVs (25.5%) in 71 patients (63.4%) demonstrated PVR, whereas 324 PVs (74.5%) exhibited PVI. The number and duration of cryoballoon applications did not differ between PVR and PVI. However, the time to PV isolation (time to effect) was considerably shorter (39.1 ± 11.7 seconds vs 67.6 ± 19.7 seconds; P < .001), the balloon temperature at time to effect was significantly warmer (-32.1°C ± 7.8°C vs -39.4°C ± 5.8°C; P < .001), the balloon nadir temperature was slightly cooler (-48.7°C ± 4.6°C vs -47.8°C ± 2.9°C; P = .034), and the total thaw time (56.5 ± 25.4 seconds vs 34.8 ± 9.1 seconds; P < .001) and interval thaw times at 0°C (iTT0; 14.8 ± 10.9 seconds vs 7.1 ± 2.0 seconds; P < .001) and 15°C (54.2 ± 25.4 seconds vs 33.3 ± 9.1 seconds; P < .001) were notably longer with PVI than with PVR. However, only a time to effect of ≤60 seconds and an iTT0 of ≥10 seconds emerged as significant predictors of PV isolation durability. Consequently, in a multivariate model, presence of both criteria predicted <1% and their mere absence ~75% likelihood of PVR. CONCLUSION: A time to effect of ≤60 seconds and an iTT0 of ≥10 seconds significantly predict PV isolation durability after the cryoballoon ablation of AF. If both criteria are met, the likelihood of PV reconnection may be exceedingly low.

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation – by protons – is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and – via the acido-antithermogenic and acido-antivasoconstrictor reflexes – modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist’s potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed.

ESTIMATES suggest that 1% or 2% of pregnant women undergo anesthesia for surgical procedures unrelated to delivery in the United States, but pregnancy may be unrecognized at the time of surgery, and there are no formal reporting mechanisms for data collection. Cerclage procedures for cervical incompetence typically are performed at the end of the first trimester. Most nonobstetric procedures result from circumstances common for the maternal age group, such as appendicitis, cholelithiasis, ovarian cysts or ovarian torsion, breast tumors, trauma, and more rarely for life-threatening cardiac or neurosurgical conditions or organ transplantation.Anesthetic considerations for surgery during pregnancy include concern for the safety of two patients, the mother and fetus. Alterations in maternal anatomy and physiology induced by pregnancy have clinical anesthetic implications and present potential hazards for the mother and fetus undergoing anesthesia. The fetus may be subjected to hazard by (1) the risk of intraoperative hypoxemia or asphyxia caused by reduced uterine blood flow, maternal hypotension, excessive maternal mechanical ventilation or maternal hypoxia, depression of the fetal cardiovascular system or central nervous system from placental passage of anesthetic agents;(2) exposure to teratogenic drugs; and (3) the risk for preterm delivery as a consequence of the surgical procedure or drugs administered. In most circumstances, the fetus is a passive recipient of anesthesia administered to the mother, suffers no blood loss, and undergoes passive changes rather than direct stress or hemodynamic alterations caused by surgery (fig. 1).During pregnancy, maternal anatomic and physiologic changes with implications for anesthetic management cause pregnant women to differ from those who are not pregnant. Although there are increased metabolic demands, these do not account for the magnitude of the increases in maternal respiratory and cardiovascular function.Minute ventilation and oxygen consumption increase and residual volume and functional residual capacity decrease; therefore, oxygen reserve decreases and pregnant women develop hypoxia and hypercapnia more rapidly with hypoventilation or apnea. Airway management by face mask, laryngeal mask, or tracheal intubation can be technically difficult in pregnant women because of increased anteroposterior chest wall diameter, breast enlargement, laryngeal edema, and weight gain that affects the soft tissues of the neck.During gestation, plasma volume and cardiac output increase, and peripheral vascular resistance decreases. From about mid-gestation, women in the supine position are at risk for aortic and venal caval compression by the gravid uterus. Physiologic compensation for aortocaval compression can be compromised by anesthetic techniques (spinal, epidural, or general) that interfere with sympathetic tone, and can result in profound hypotension. For these women, avoiding the supine position by displacing the uterus laterally is important.Pregnancy is associated with decreased anesthetic requirements: The minimum alveolar concentration decreases, 1and pregnant women may be more susceptible to axonal block by local anesthetics for reasons that remain unclear.Because of mechanical and hormonal changes, pregnant women are at increased risk for gastric acid aspiration with anesthetic induction or unconscious sedation. Gastroesophageal sphincter tone is reduced, and although gastric motility remains normal during gestation, it is significantly impaired by opioid administration, onset of labor, pain, trauma, and so forth. For fasted pregnant women in the second or third trimester, or those with a history of reflux esophagitis, I advocate induction of general anesthesia using techniques for “full stomach precautions.”To ensure fetal well-being, decreases in uterine blood flow or its oxygen content must be avoided. In addition, excessive maternal mechanical hyperventilation can reduce venous return and thereby cardiac output, which reduces uterine blood flow. The asphyxiated fetus cannot increase oxygen extraction; rather, compensation is by redistribution of blood flow to vital organs. The uterine circulation is not autoregulated; it represents approximately 10% of cardiac output by full-term gestation and remains sensitive to vasopressors. Vasoactive medication that reduces uterine blood flow, such as α-adrenergic agents, dopamine, or epinephrine, are not ideal agents for treating maternal hypotension; although blood pressure may increase, uterine blood flow may remain depressed. 2However, small doses of phenylephrine have been used safely in several studies and reported cases; I consider it an agent of second choice when ephedrine is ineffective or when the mother is tachycardic, has a stenotic valvular cardiac lesion, or receives β-agonist therapy. Besides uterine displacement, fluid bolus, Trendelenburg position, leg elevation, the use of compression stockings, or any combination of these, ephedrine remains the agent of choice in the initial pharmacologic management of maternal hypotension. 3Maternal administration of increased inspired oxygen will increase fetal oxygenation; however, the fetus is never at risk for hyperoxia, because fetal oxygen tension will not exceed approximately 65 mmHg, even with maternal administration of 100% oxygen.Despite the far greater risk to the fetus from maternal hypotension or hypoxia, considerable concern exists about the potential for anesthetic agents or adjuvants to result in abortion or have teratogenic effects. For a defect to be produced, the embryo, fetus, or newborn must be exposed to a teratogenic agent at a given dose during a particular developmental stage in a species or person with a particular genetic susceptibility. Each organ and each system undergoes a critical stage of differentiation during which vulnerability to teratogens is greatest and specific malformations can be produced.Clinical concentrations of volatile anesthetics have wide-ranging cellular effects, some of which may be potentially harmful to developing cells. Furthermore, it has been shown that nitrous oxide inactivates methionine synthetase, which in turn inhibits the synthesis of thymidine and DNA, inhibits cell division, and potentially disrupts other biochemical pathways in methylation reactions. The concern is whether these known cellular effects of anesthetic agents are teratogenic.To date, no clinical data link these cellular actions with teratogenic outcomes. Investigations of anesthetic teratogenicity have included studies of anesthetic agents on reproduction in rodents, epidemiologic surveys of chronic occupational exposure to trace concentrations of anesthetic agents, and outcome studies of women who have undergone surgery during pregnancy. 4–6Laboratory investigations of the teratogenicity of inhalation agents in rodents suggest that modern volatile anesthetics in trace and subanesthetic concentrations do not result in adverse reproductive or teratogenic effects. Nitrous oxide is a weak teratogen in rodents when administered for long periods. However, the coadministration of halothane or isoflurane reverses the fetal lethality and teratogenic actions of nitrous oxide without affecting methionine synthetase activity. 7The reasons for these findings are uncertain, but they may be related to the vasoconstricting properties of nitrous oxide. Nitrous oxide appears to be weakly teratogenic in rodents for biochemical reasons unrelated to its inactivation of methionine synthetase.Large survey studies that considered outcomes in women who underwent surgery during pregnancy suggest no increase in congenital anomalies among their offspring, but rather an increase in the risk for abortions, growth restriction, and increased frequency of low and very low birth-weight neonates for reasons attributed to the requirement for surgery but not anesthetic administration. 8,9Some smaller retrospective studies suggest an association with neural tube defects and first-trimester anesthesia exposure. 10,11These studies do not allow us to conclude categorically that anesthetic agents are not teratogenic in humans. However, the patient's primary disease, site of surgery, or surgical procedure is more likely to increase the risk for abortion than is exposure to anesthesia.Although many pregnant women undergo anesthesia and many others are exposed by occupation to anesthetics every year, the teratogenic risk of anesthetic agents in humans must be assessed based on incomplete data. Available studies suggest, for a surgical procedure, that administration of nitrous oxide or volatile, opioid, regional, or local anesthetics to pregnant women will not have deleterious effects on embryonic or fetal development and lack clinical significance for adverse neonatal outcome. The danger of teratogenic effects from currently available anesthetic or sedative drugs remains only a potential risk. No anesthetic, opioid analgesic, sedative-hypnotic, or anxiolytic agent appears to be teratogenic or safer than another agent. The long-standing relative contraindication and concern about benzodiazepine use, particularly in the first trimester, was recently dispelled. 12I use preoperative medication for women to treat pain or anxiety, as appropriate. Catecholamines increased by pain or anxiety may adversely effect uterine blood flow. 13Neuromuscular blocking agents do not cross the placental barrier in clinically significant amounts. Although pregnant women have decreased concentrations of plasma cholinesterase and increased volumes for drug distribution, they may have relatively decreased hepatic blood flow. Therefore, the onset, duration, and clearance for neuromuscular blocking agents may be altered and are best administered with neuromuscular monitoring. Reversal agents should be administered slowly to avoid acute increases in acetylcholine, which might stimulate uterine contractions.Although some data suggest that sodium nitroprusside may cause cyanide toxicity in laboratory animals, the doses used in experiments far exceeded safe clinical doses. Nitroprusside has been used safely in pregnant women, as has been nitroglycerin. Acute administration of β-adrenergic blocking agents is also safe, although long-term use has been associated with intrauterine growth restriction. High-dose administration of esmolol or other beta-blocking agents has been associated with fetal bradycardia, but these agents are not contraindicated during pregnancy.Data from the Swedish Health Registry confirms the safety of laparoscopy during the first half of gestation, 14and there are several case reports of success in the late second and early third trimesters. Recommended precautions include use of pneumatic stockings to promote venous return, use of ultrasound rather than cholangiograms for cholecystectomy, use of nitrous oxide instead of carbon dioxide for pneumoperitoneum, avoidance of fetal respiratory acidosis, and use of the lowest-pressure pneumoperitoneum possible to avoid exacerbating vena caval compression.When intentional manipulation of the maternal cardiovascular system is anticipated, such as deliberate hypotensive techniques or cardiopulmonary bypass, or when extraordinary procedures are undertaken, such as fetal surgery, it is wise to consult directly with those who have had more experience. In these cases, fetal monitoring is essential to ensure the adequacy of placental perfusion and optimization of the intrauterine environment.Whenever possible, the fetus should be shielded from radiographic exposure (American College of Obstetricians and Gynecologists, Technical Bulletin #158, 1995).Surgery and anesthesia can affect uterine activity and placental perfusion, and therefore fetal oxygenation and fetal heart rate. Fetal heart rate can also be affected directly by medications that readily cross the placenta or indirectly by their influence on maternal hemodynamics. Maternal anesthesia, and thus fetal anesthesia, and maternal (and hence fetal) hypothermia may decrease baseline fetal heart rate and beat-to-beat variability, but it will not cause spontaneous decelerations or those in response to a uterine contraction. The latter would be signs of fetal stress (hypoxemia, asphyxia).Fetal and uterine monitoring during surgery is often possible, but in some circumstances access may be difficult. During surgery, steps can be taken to improve uterine perfusion and fetal oxygenation if they are compromised. However, such monitoring may be impractical in emergent or urgent situations, has not been documented to improve fetal outcome, and requires expertise often not possessed by regular intraoperative personnel. Misinterpretations could lead to unsafe interventions. When used, appropriate personnel trained in basic fetal heart rate interpretation should be immediately available. Although not considered a necessity for the intraoperative management of most pregnant surgical patients, preoperative and postoperative monitoring of uterine activity and fetal heart rate is advocated.I recommend fetal monitoring whenever possible, particularly for the viable-age fetus and when the surgical procedure is major (e.g. , laparotomy), rather than minor (e.g. , carpal tunnel release). When monitoring by external abdominal ultrasound is not logistically feasible, I have used a sterile sleeve on a transabdominal ultrasound transducer, and once a transesophageal echocardiography probe placed directly on the uterus. Another alternative is a transvaginal ultrasound probe, particularly in early gestation.Elective procedures, other than postpartum tubal ligations, should be deferred until approximately 6 weeks after delivery, when the physiologic changes of pregnancy have passed and fetal well-being is no longer a concern (fig. 2). Women of child-bearing age should be asked about their last menstrual period, informed of potential risks, and pregnancy testing offered if their menstrual history is uncertain or they request it to avoid elective procedures during early gestation. Despite the lack of clinical evidence, delaying surgery until the second trimester, when possible, may reduce the risks for teratogenicity and spontaneous abortion. Whenever major surgery is undertaken in the pregnant patient, a perinatologist or obstetrician should be consulted to assist in perioperative management, diagnose and manage possible preterm labor, and to try to avoid preterm delivery. Informing the obstetrician or perinatologist of any surgical procedure may be in the best interest of the patient.

OBJECTIVE: Evaluate changes in condomless anal sex at last sex among men who have sex with men (MSM) and assess if these changes are associated with the adoption of serosorting and biomedical prevention. DESIGN: The National HIV Behavioral Surveillance is a crosssectional survey done in up to 21 cities in 2005, 2008, 2011 and 2014. METHODS: MSM were recruited through venue-based sampling. Among men reporting at least one male partner, we evaluated changes in condomless anal sex at last sex with a partner with (1) HIV-concordant (proxy for serosorting) or (2) HIV-discordant (discordant/unknown) status. We hypothesized that if concordant condomless sex was increasing while discordant was stable/declining, the increases could be driven by more men attempting to serosort. We used generalized estimating equations assuming a Poisson distribution and robust variance estimator to explore whether temporal changes in the outcomes varied by selected characteristics. We also assessed changes in condomless anal sex by antiretroviral therapy (ART) use among HIV-positive MSM. RESULTS: Among 5371 HIV-positive MSM, there were increases in concordant (19% in 2005 to 25% in 2014, P < 0.001) and discordant condomless sex (15 to 19%, P < 0.001). The increases were not different by ART use. Among 30 547 HIV-negative MSM, concordant (21 to 27%, P < 0.001) and discordant condomless sex (8 to 13%, P < 0.001) increased. CONCLUSION: Our data suggest that condom use decreased among MSM and that the trends are not explained by serosorting or ART. Promotion of condoms and increased access to preexposure prophylaxis are vital to ensure that the benefits of ART in reducing transmission of HIV are not undermined.