Anesthesia & Analgesia

Gene Variants in Hepatic Metabolism, Gamma-Aminobutyric Acid-ergic Reward, and Prostaglandin Pathways in Opioid-Consuming and Opioid-Naïve Patients Presenting for Lower Extremity Total Joint Replacement Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways. Accepted for publication May 14, 2019. Funding: Departmental/institutional. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). Clinical trial number and registry URL: This study is not subject to clinicaltrials.gov review as the study is not a clinical trial and does not involve an intervention or investigational use of a device or drug. Reprints will not be available from the authors. Address correspondence to Ami R. Stuart, PhD, Department of Anesthesiology, University of Utah, 30 N 1900 E RM 3C444, Salt Lake City, UT 84112. Address e-mail to ami.stuart@hsc.utah.edu. © 2019 International Anesthesia Research Society

Adultification of Black Children in Pediatric Anesthesia BACKGROUND: Unconscious racial bias in anesthesia care has been shown to exist. We hypothesized that black children may undergo inhalation induction less often, receive less support from child life, have fewer opportunities to have a family member present for induction, and receive premedication with oral midazolam less often. METHODS: We retrospectively collected data on those <18 years of age from January 1, 2012 to January 1, 2018 including age, sex, race, height, weight, American Society of Anesthesiologists (ASA) physical status, surgical service, and deidentified anesthesiology attending physician. Outcome data included mask versus intravenous induction, midazolam premedication, child life consultation, and family member presence. Racial differences between all outcomes were assessed in the cohort using a multivariable logistic regression model. RESULTS: A total of 33,717 Caucasian and 3901 black children were eligible for the study. For the primary outcome, black children 10–14 years were 1.3 times more likely than Caucasian children to receive mask induction (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.1–1.6; P = .001). Child life consultation was poorly documented (<0.5%) and not analyzed. Black children <15 years of age were at least 31% less likely than Caucasians to have a family member present for induction (AOR range, 0.4–0.6; 95% CI range, 0.31–0.84; P < .010). Black children <5 years of age were 13% less likely than Caucasians to have midazolam given preoperatively (AOR, 0.9; 95% CI, 0.8–0.9; P = .012). CONCLUSIONS: This study suggests that disparities in strategies for mitigating anxiety in the peri-induction period exist and adultification may be 1 cause for this bias. Black children 10 to 14 years of age are 1.3 times as likely as their Caucasian peers to be offered inhalation induction to reduce anxiety. However, black children are less likely to receive premedication with midazolam in the perioperative period or to have family members present at induction. The cause of this difference is unclear, and further prospective studies are needed to fully understand this difference. Accepted for publication May 7, 2019. Funding: None. The authors declare no conflicts of interest. This report describes human research. Institutional review board (IRB) contact information: Institutional Review Boards of the UM Medical School, 2800 Plymouth Rd, Building 200, Room 2086, Ann Arbor, MI 48109; e-mail: irbmed@umich.edu. The requirement for written informed consent was waived by the IRB. This report describes an observational clinical study. The author states that the report includes every item in the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) checklist for case–control observational clinical studies. Reprints will not be available from the authors. Address correspondence to Anne Baetzel, MD, Department of Anesthesiology, University of Michigan Medical School, 4–911 CS Mott Children's Hospital, 1540 E Medical Center Dr, Ann Arbor, MI 48109. Address e-mail to abaetzel@med.umich.edu. © 2019 International Anesthesia Research Society

Anesthesia Provider Training and Practice Models: A Survey of Africa BACKGROUND: In Africa, most countries have fewer than 1 physician anesthesiologist (PA) per 100,000 population. Nonphysician anesthesia providers (NPAPs) play a large role in the workforce of many low- and middle-income countries (LMICs), but little information has been systematically collected to describe existing human resources for anesthesia care models. An understanding of existing PA and NPAP training pathways and roles is needed to inform anesthesia workforce planning, especially for critically underresourced countries. METHODS: Between 2016 and 2018, we conducted electronic, phone, and in-person surveys of anesthesia providers in Africa. The surveys focused on the presence of anesthesia training programs, training program characteristics, and clinical scope of practice after graduation. RESULTS: One hundred thirty-one respondents completed surveys representing data for 51 of 55 countries in Africa. Most countries had both PA and NPAP training programs (57%; mean, 1.6 pathways per country). Thirty distinct training pathways to become an anesthesia provider could be discriminated on the basis of entry qualification, duration, and qualification gained. Of these 30 distinct pathways, 22 (73%) were for NPAPs. Physician and NPAP program durations were a median of 48 and 24 months (ranges: 36–72, 9–48), respectively. Sixty percent of NPAP pathways required a nursing background for entry, and 60% conferred a technical (eg, diploma/license) qualification after training. Physicians and NPAPs were trained to perform most anesthesia tasks independently, though few had subspecialty training (such as regional or cardiac anesthesia). CONCLUSIONS: Despite profound anesthesia provider shortages throughout Africa, most countries have both NPAP and PA training programs. NPAP training pathways, in particular, show significant heterogeneity despite relatively similar scopes of clinical practice for NPAPs after graduation. Such heterogeneity may reflect the varied needs and resources for different settings, though may also suggest lack of consensus on how to train the anesthesia workforce. Lack of consistent terminology to describe the anesthesia workforce is a significant challenge that must be addressed to accelerate workforce research and planning efforts. Accepted for publication May 16, 2019. Funding: This work received funding Hellman Family Foundation and received additional funds from the International Relations Committee of the Association of Anaesthetists/Royal College of Anesthetists for travel support. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). T. J. Law and F. Bulamba contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Tyler J. Law, MD, Division of Global Health Equity, Department of Anesthesia and Perioperative Care, University of California San Francisco, 1001 Potrero Ave, Bldg 5, Rm 3C38, San Francisco, CA 94110. Address e-mail to tyler.law@ucsf.edu. © 2019 International Anesthesia Research Society

Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·V·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; V: respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L−1 (15.53 µg·L−1; median: 2.11 µg·L−1, interquartile range [IQR]: 4.58 µg·L−1) and in all postoperative samples (25.42 µg·L−1 [21.39 µg·L−1]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (β = 216.89; P < .001) and to the calculated masses of inhaled SEVO (β = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting. Accepted for publication May 16, 2019. Funding: Departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jennifer Herzog-Niescery, MD, Department of Anesthesiology, Ruhr-University Bochum, St Josef-Hospital Bochum, Gudrunstraße 56, D-44791 Bochum, Germany. Address e-mail to j.herzog-niescery@klinikum-bochum.de © 2019 International Anesthesia Research Society

Impact of Anesthetics, Analgesics, and Perioperative Blood Transfusion in Pediatric Cancer Patients: A Comprehensive Review of the Literature Cancer is the leading cause of death by disease in developed countries. Children and adolescents with cancer need surgical interventions (ie, biopsy or major surgery) to diagnose, treat, or palliate their malignancies. Surgery is a period of high vulnerability because it stimulates the release of inflammatory mediators, catecholamines, and angiogenesis activators, which coincides with a period of immunosuppression. Thus, during and after surgery, dormant tumors or micrometastasis (ie, minimal residual disease) can grow and become clinically relevant metastasis. Anesthetics (ie, volatile agents, dexmedetomidine, and ketamine) and analgesics (ie, opioids) may also contribute to the growth of minimal residual disease or disease progression. For instance, volatile anesthetics have been implicated in immunosuppression and direct stimulation of cancer cell survival and proliferation. Contrarily, propofol has shown in vitro anticancer effects. In addition, perioperative blood transfusions are not uncommon in children undergoing cancer surgery. In adults, an association between perioperative blood transfusions and cancer progression has been described for some malignancies. Transfusion-related immunomodulation is one of the mechanisms by which blood transfusions can promote cancer progression. Other mechanisms include inflammation and the infusion of growth factors. In the present review, we discuss different aspects of tumorigenesis, metastasis, angiogenesis, the immune system, and the current studies about the impact of anesthetics, analgesics, and perioperative blood transfusions on pediatric cancer progression. Accepted for publication May 23, 2019. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Juan P. Cata, MD, Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Centre, 1515 Holcombe Blvd, Unit 409, Houston, TX 77005. Address e-mail to jcata@mdanderson.org. © 2019 International Anesthesia Research Society

In Response No abstract available

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients. Accepted for publication May 20, 2019. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael G. Richardson, MD, Division of Obstetric Anesthesiology, Vanderbilt University Medical Center, 4202 VUH, Nashville, TN 37232. Address e-mail to m.richardson@vumc.org. © 2019 International Anesthesia Research Society

BOSTN Bundle Intervention for Perioperative Screening and Management of Patients With Suspected Obstructive Sleep Apnea: A Hospital Registry Study BACKGROUND: We developed and implemented a perioperative guideline for obstructive sleep apnea (OSA), comprising a preoperative screening tool (BOSTN) and clinical management pathways. OSA was suspected with 2 or more of the following: body mass index ≥30 kg/m2, observed apnea, loud snoring, daytime tiredness, and neck circumference ≥16.5 inches in women or ≥ 17.5 inches in men. The primary objective of this study was to assess the association between high BOSTN scores and the requirement of invasive mechanical ventilation after surgery. METHODS: In this hospital registry study, 169,662 noncardiac surgical cases performed at Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, between May 2008 and September 2017 were analyzed. We assessed the association between a high BOSTN Score (score ≥2) and the primary outcome of requirement of invasive mechanical ventilation within 7 days after surgery using multivariable logistic regression adjusted for patient-specific factors and case-specific surgical and anesthesiological confounders. Patients with a BOSTN Score ≥2 were assumed to have a high likelihood of suffering from OSA. Key secondary outcome was postoperative desaturation, defined as a peripheral oxygen saturation measurement <90% within 10 minutes of extubation. RESULTS: Invasive mechanical ventilation within 7 days of surgery was necessary in 3170 (2.3%) low-risk cases (BOSTN Score <2) and 664 (2.1%) high-risk cases (BOSTN Score ≥2). A score ≥2 was associated with significantly lower odds of requiring postoperative invasive ventilation (adjusted odds ratio [aOR], 0.89; 95% confidence interval [CI], 0.80–0.98; P = .017), but with an increased risk of postextubation desaturation (aOR, 1.34; 99.3% CI, 1.21–1.48; P < .001). Patients with a score ≥2 were hospitalized for an average of 3.71 days after surgery, compared to 4.27 days with a score <2 (adjusted incidence rate ratio [aIRR], 0.87; 99.3% CI, 0.84–0.91; P < .001). CONCLUSIONS: Patients at high risk of OSA required postoperative mechanical ventilation less frequently, had higher odds of postoperative desaturation, and were hospitalized for shorter periods of time. Accepted for publication May 14, 2019. Funding: M.E. receives unrestricted funds from philanthropic donors Jeffrey and Judy Buzen. E.S. receives departmental funding from the Department of Anesthesia, Critical Care and Pain Medicine at Beth Israel Deaconess Medical Center, Boston. All other authors have no financial disclosures. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). D. Raub and P. Santer contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Eswar Sundar, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. Address e-mail to esundar@bidmc.harvard.edu. © 2019 International Anesthesia Research Society

Delivery Hospital Characteristics and Postpartum Maternal Mortality: A National Case–Control Study in France BACKGROUND: The variability in resources for managing critical events among maternity hospitals may impact maternal safety. Our main objective was to assess the risk of postpartum maternal death according to hospitals' organizational characteristics. A secondary objective aimed to assess the specific risk of death due to postpartum hemorrhage (PPH). METHODS: This national population-based case–control study included all 2007–2009 postpartum maternal deaths from the national confidential enquiry (n= 147 cases) and a 2010 national representative sample of parturients (n = 14,639 controls). To adjust for referral bias, cases were classified by time when the condition/complication responsible for the death occurred: postpartum maternal deaths due to conditions present before delivery (n = 66) or during or after delivery (n = 81). Characteristics of delivery hospitals included 24/7 on-site availability of an anesthesiologist and an obstetrician, level of perinatal care, number of deliveries annually, and their teaching and profit status. In teaching and other nonprofit hospitals in France, obstetric care is organized on the principle of collective team-based management, while in for-profit hospitals, this organization is based mostly on that of "one woman–one doctor." Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for postpartum maternal death. RESULTS: The risk of maternal death from prepartum conditions was lower for women who gave birth in for-profit compared with teaching hospitals (aOR, 0.3; 95% CI, 0.1–0.8; p = .02) and in hospitals with <1500 vs ≥1500 annual deliveries (aOR, 0.4; 95% CI, 0.1–0.9; P = .02). Conversely, the risk of postpartum maternal death from complications occurring during or after delivery was higher for women who delivered in for-profit compared with teaching hospitals (aOR, 2.8; 95% CI, 1.3–6.0; P = .009), as was the risk of death from PPH in for-profit versus nonprofit hospitals (aOR, 2.8; 95% CI, 1.2–6.5; P = .019). CONCLUSIONS: After adjustment for the referral bias related to prepartum morbidity, the risk of postpartum maternal mortality in France differs according to the hospital's organizational characteristics. Accepted for publication May 10, 2019. Funding: This work was funded by the French Institute for Public Health Research (IReSP). The French confidential enquiry into maternal deaths is funded by the French Institute for Public Health Surveillance (InVS) and the French National Institute of Health and Medical Research (Inserm). The French National Perinatal Survey was funded by the Ministry of Health. The French National Perinatal Survey was funded by the Ministry of Health. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anesthesia-analgesia.org). A full list of contributors can be found at the end of the article. Reprints will not be available from the authors. Address correspondence to Monica Saucedo, MD, PhD, Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, Maternité Port-Royal 6ème étage, 53 Avenue de l'Observatoire, 75014 Paris, France. Address e-mail to monica.saucedo@inserm.fr. © 2019 International Anesthesia Research Society

Functional MRI: Basic Principles and Emerging Clinical Applications for Anesthesiology and the Neurological Sciences No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cancer Causes & Control

Healthy dietary patterns and risk and survival of breast cancer: a meta-analysis of cohort studies Abstract Purposes Dietary patterns have been found to be associated with the overall cancer risk and survival. However, the associations of healthy dietary patterns and breast cancer remain unclear. We aimed to conduct a meta-analysis of prospective cohort studies to estimate the pooled results of the association of healthy dietary patterns with breast cancer risk and survival. Methods PubMed, EMBASE, and Web of Science were searched for literature published until June 24th, 2018 that examined the associations between healthy dietary patterns and breast cancer risk and survival. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by using a random-effects model for meta-analysis. Results There were 32 articles retrieved for the meta-analysis, with 27 for breast cancer risk and five for breast cancer survival. There was a statistically significant lower risk of breast cancer associated with healthy dietary patterns (RR = 0.93, 95% CI: 0.88, 0.98). Subgroup analysis results suggested that there was an inverse association between breast cancer risk and posterori-derived healthy patterns, but no statistically significant associations were found in other stratified subgroups (a priori-derived diet, study region, menopausal status, or breast cancer subtypes). Healthy dietary patterns were associated inversely with all-cause mortality (RR = 0.76, 95% CI: 0.63, 0.92); however, no association was found for breast cancer-specific mortality. Conclusions The results suggested that healthy dietary patterns might be associated with a reduced risk of breast cancer and all-cause mortality among breast cancer patients. It could be clinically relevant to promote healthy dietary patterns for breast cancer prevention and improve survival among breast cancer patients.

The association between coffee consumption and bladder cancer in the bladder cancer epidemiology and nutritional determinants (BLEND) international pooled study Abstract Background Inconsistent results for coffee consumption and bladder cancer (BC) risk have been shown in epidemiological studies. This research aims to increase the understanding of the association between coffee consumption and BC risk by bringing together worldwide case–control studies on this topic. Methods Data were collected from 13 case–control comprising of 5,911 cases and 16,172 controls. Pooled multivariate odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models. Furthermore, linear dose–response relationships were examined using fractional polynomial models. Results No association of BC risk was observed with coffee consumption among smokers. However, after adjustment for age, gender, and smoking, the risk was significantly increased for never smokers (ever vs. never coffee consumers: ORmodel2 1.30, 95% CI 1.06–1.59; heavy (> 4 cups/day) coffee consumers vs. never coffee consumers: ORmodel2 1.52, 95% CI 1.18–1.97, p trend = 0.23). In addition, dose–response analyses, in both the overall population and among never smokers, also showed a significant increased BC risk for coffee consumption of more than four cups per day. Among smokers, a significant increased BC risk was shown only after consumption of more than six cups per day. Conclusion This research suggests that positive associations between coffee consumption and BC among never smokers but not smokers.

Proceedings of the fourth international molecular pathological epidemiology (MPE) meeting Abstract An important premise of epidemiology is that individuals with the same disease share similar underlying etiologies and clinical outcomes. In the past few decades, our knowledge of disease pathogenesis has improved, and disease classification systems have evolved to the point where no complex disease processes are considered homogenous. As a result, pathology and epidemiology have been integrated into the single, unified field of molecular pathological epidemiology (MPE). Advancing integrative molecular and population-level health sciences and addressing the unique research challenges specific to the field of MPE necessitates assembling experts in diverse fields, including epidemiology, pathology, biostatistics, computational biology, bioinformatics, genomics, immunology, and nutritional and environmental sciences. Integrating these seemingly divergent fields can lead to a greater understanding of pathogenic processes. The International MPE Meeting Series fosters discussion that addresses the specific research questions and challenges in this emerging field. The purpose of the meeting series is to: discuss novel methods to integrate pathology and epidemiology; discuss studies that provide pathogenic insights into population impact; and educate next-generation scientists. Herein, we share the proceedings of the Fourth International MPE Meeting, held in Boston, MA, USA, on 30 May–1 June, 2018. Major themes of this meeting included 'integrated genetic and molecular pathologic epidemiology', 'immunology-MPE', and 'novel disease phenotyping'. The key priority areas for future research identified by meeting attendees included integration of tumor immunology and cancer disparities into epidemiologic studies, further collaboration between computational and population-level scientists to gain new insight on exposure-disease associations, and future pooling projects of studies with comparable data.

The sensitivity of reported effects of EMF on childhood leukemia to uncontrolled confounding by residential mobility: a hybrid simulation study and an empirical analysis using CAPS data Abstract Purpose Residential mobility is considered as a potential source of confounding in studies assessing environmental exposures, including in studies of electromagnetic field (EMF) exposures and childhood leukemia. Methods We present a hybrid simulation study where we simulate a synthetic dataset based on an existing study and use it to assess the sensitivity of EMF–leukemia associations to different scenarios of uncontrolled confounding by mobility under two major hypotheses of the infectious etiology of childhood leukemia. We then used the findings to conduct sensitivity analysis and empirically offset the potential bias due to unmeasured mobility in the California Power Line Study dataset. Results As expected, the stronger the assumed relationship between mobility and exposure and outcome, the greater the potential bias. However, no scenario created a bias strong enough to completely explain away previously observed associations. Conclusions We conclude that uncontrolled confounding by residential mobility had some impact on the estimated effect of EMF exposures on childhood leukemia, but that it was unlikely to be the primary explanation behind previously observed largely consistent, but unexplained associations.

The association of marital status and mortality among men with early-stage prostate cancer treated with radical prostatectomy: insight into post-prostatectomy survival strategies Abstract Purpose The purpose of this study was to determine the association of marital status, a marker of social support, with all-cause and prostate cancer-specific mortality in a cohort of men with early-stage prostate cancer treated with radical prostatectomy. Methods We conducted a retrospective cohort study of 3,579 men treated for localized (stage 1–2) prostate cancer with radical prostatectomy at a single institution between 1994 and 2004. Marital status (not married vs. married) and marital history (never married, divorced, widowed vs. married) at the time of prostatectomy were examined in relation to (1) all-cause mortality and (2) prostate cancer-specific mortality using Cox proportional hazards regression. Results Not being married (vs. married) at the time of radical prostatectomy was associated with an increased risk of all-cause mortality [Hazard Ratio (HR) 1.42; 95% Confidence Interval (CI) 1.10, 1.85]. Similarly, in analyses of marital history, never-married men were at highest risk of all-cause mortality (HR 1.77, 95% CI 1.19, 2.63). Unmarried status (vs. married) was also associated with an increased risk of prostate cancer-specific mortality (HR 1.97; 95% CI 1.01, 3.83). Conclusions Unmarried men with prostate cancer were at greater risk for death after radical prostatectomy. Among married men with prostate cancer, marriage likely serves as a multi-faceted proxy for many protective factors including social support. Future studies should explore the mechanisms underlying these findings to inform the development of novel prostate cancer survival interventions for unmarried men and those with low social support.

Soy and tea intake on cervical cancer risk: the Singapore Chinese Health Study Abstract Purpose Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women. Methods The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.7 years of follow-up and 312 incident cervical cancer cases. Multivariable proportional hazard models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of cervical cancer associated with intake levels of soy and tea. Results High intake of soy alone was associated with a statistically borderline significant 20% reduced risk of cervical cancer (HR 0.80, 95% CI 0.61, 1.05) while green tea alone was not (HR 0.97, 95% CI: 0.76, 1.22). In stratified analysis, high intake of soy was associated with a statistically significant decrease in cervical cancer risk among green tea drinkers (HR 0.43; 95% CI 0.28, 0.69) but not among non-drinkers of green tea. The difference in the soy-cervical cancer risk association between green tea drinkers and non-drinkers was statistically significant (p for interaction = 0.004). This inverse association between soy intake and cervical cancer risk remained after further adjustment for human papillomavirus serostatus. Black tea consumption was not associated with cervical cancer risk. Conclusions These findings suggest that a protective effect of soy against cervical cancer development may depend on green tea constituents.

Association between greater leg length and increased incidence of colorectal cancer: the atherosclerosis risk in communities (ARIC) study Abstract Purpose Previous studies have reported that taller people have an increased risk of colorectal cancer (CRC). We examined the association of two height components—leg length and sitting height—with CRC risk in 14,532 individuals aged 45–64 years in the Atherosclerosis Risk in Communities study. Methods Anthropometrics were measured at baseline (1987–1989). Incident CRC cases (n = 382) were ascertained from 1987 to 2012. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios for CRC and colon cancer across quintiles of sex-specific leg length and sitting height. Results The highest (versus the lowest) quintile of leg length was associated with a 36% greater CRC risk (p-trend = 0.04), and 51% greater colon cancer risk (p-trend = 0.01). For the top four quintiles combined, risk was increased by 34% for CRC and by 45% for colon cancer versus the lowest quintile. Total height and sitting height were not significantly associated with CRC or colon cancer risk. A small number of cases (n = 57) limited our ability to conduct subgroup analyses for rectal cancer. Conclusions A positive association of leg length with CRC and colon cancer risk suggests that biological mechanisms leading to greater leg length during puberty may explain the association between taller height and CRC.

Cost-effectiveness of breast cancer screening in the National Breast and Cervical Cancer Early Detection Program Abstract Purpose To estimate the cost-effectiveness of breast cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Methods Using a modified CISNET breast cancer simulation model, we estimated outcomes for women aged 40–64 years associated with three scenarios: breast cancer screening within the NBCCEDP, screening in the absence of the NBCCEDP (no program), and no screening through any program. We report screening outcomes, cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and sensitivity analyses results. Results Compared with no program and no screening, the NBCCEDP lowers breast cancer mortality and improves QALYs, but raises health care costs. Base-case ICER for the program was $51,754/QALY versus no program and $50,223/QALY versus no screening. Probabilistic sensitivity analysis ICER for the program was $56,615/QALY [95% CI $24,069, $134,230/QALY] versus no program and $51,096/QALY gained [95% CI $26,423, $97,315/QALY] versus no screening. Conclusions On average, breast cancer screening in the NBCCEDP was cost-effective compared with no program or no screening.

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis Abstract Purpose To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). Methods We used harmonized data from 13 case–control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. Results Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65–0.83) but not women (OR 0.92; 95% CI 0.83–1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45–0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72–0.98) studies. Conclusions In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.

The effect of delivery structure on costs, screening and health promotional services in state level National Breast and Cervical Cancer Early Detection Programs Abstract Purpose We estimated the costs and effectiveness of state programs in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) based on the type of delivery structure. Methods Programs were classified into three delivery structures: (1) centralized, (2) decentralized, and (3) mixed. Centralized programs offer clinical services in satellite offices, but all other program activities are performed centrally. Decentralized programs contract with other entities to fully manage and provide screening and diagnostic services and other program activities. Programs with mixed service delivery structures have both centralized and decentralized features. Programmatic costs were averaged over a 3 year period (2006–2007, 2008–2009, and 2009–2010). Effectiveness was defined in terms of the average number of women served over the 3 years. We report costs per woman served by program activity and delivery structure and incremental cost effectiveness by program structure and by breast/cervical services. Results Average costs per woman served were lowest for mixed program structures (breast = $225, cervical = $216) compared to decentralized (breast = cervical = $276) and centralized program structures (breast = $259, cervical = $251). Compared with decentralized programs, for each additional woman served, centralized programs saved costs of $281 (breast) and $284 (cervical). Compared with decentralized programs, for each additional woman served, mixed programs added an additional $109 cost for breast but saved $1,777 for cervical cancer. Conclusions Mixed program structures were associated with the lowest screening and diagnostic costs per woman served and had generally favorable incremental costs relative to the other program structures.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Gastroenterology

The Utility of Esophageal Motility Testing in Gastroesophageal Reflux Disease (GERD) Abstract Purpose of Review Here, we discuss how esophageal motor testing plays important roles in patients with suspected gastroesophageal reflux disease (GERD). In addition to guiding appropriate placement of catheters for ambulatory reflux monitoring, esophageal high-resolution manometry (HRM) rules out confounding diagnoses, such as achalasia spectrum disorders, that can present with symptoms similar to that of GERD, but are managed very differently. Recent Findings HRM performed with impedance in the post-prandial setting (PP-HRIM) can assess for rumination syndrome or supragastric belching, which should be directed towards behavioral interventions. The recent GERD Classification of Motor Function recommends a hierarchical approach, focusing on (1) the esophagogastric junction (EGJ), (2) the esophageal body, and (3) esophageal contraction reserve, which can be assessed with provocative maneuvers at HRM, such as multiple rapid swallows (MRS). This approach can inform the appropriate tailoring of antireflux surgery. Novel esophageal motility metrics, such as the EGJ-contractile integral from HRM, or post-reflux swallow-induced peristaltic wave indices from 24-h pH-impedance monitoring, may also assist with GERD diagnosis. Summary Assessment of esophageal motor function can contribute in a significant manner to the care of patients with suspected GERD, particularly when esophageal symptoms do not improve with antisecretory therapy, and/or when surgical or endoscopic antireflux therapies are under consideration.

Duodenal Chemosensing of Short-Chain Fatty Acids: Implications for GI Diseases Abstract Purpose of Review Short-chain fatty acids (SCFAs), the main bacterial fermentation products in the hindgut of hindgut fermenters, are also present in the foregut lumen. We discuss the impact of SCFAs in the duodenal defense mechanisms and in the gastrointestinal (GI) pathogenesis. Recent Findings Luminal SCFAs augment the duodenal mucosal defenses via release of serotonin (5-HT) and glucagon-like peptide-2 (GLP-2) from enteroendocrine cells. Released GLP-2 protects the small intestinal mucosa from nonsteroidal anti-inflammatory drug-induced enteropathy. SCFAs are also rapidly absorbed via SCFA transporters and interact with afferent and myenteric nerves. Excessive SCFA signals with 5-HT3 receptor overactivation may be implicated in the pathogenesis of irritable bowel syndrome symptoms. SCFA production exhibits diurnal rhythms with host physiological responses, suggesting that oral SCFA treatment may adjust the GI clocks. Summary SCFAs are not only a source of energy but also signaling molecules for the local regulation of the GI tract and systemic regulation via release of gut hormones. Targeting SCFA signals may be a novel therapeutic for GI diseases and metabolic syndrome.

Gastroduodenal Injury: Role of Protective Factors Abstract Purpose of Review The gastroduodenal mucosal layer is a complex and dynamic system that functions in an interdependent manner to resist injury. We review and summarize the most updated knowledge about gastroduodenal defense mechanisms and specifically address (a) the mucous barrier, (b) membrane and cellular properties, and vascular, hormonal, and (c) gaseous mediators. Recent Findings Trefoil factor family peptides play a crucial role in cellular restitution by increasing cellular permeability and expression of aquaporin channels, aiding cellular migration and tissue repair. Additionally, evidence suggests that the symptoms of functional dyspepsia may be attributed to alterations in the duodenum, including low-grade inflammation and increased mucosal permeability. Summary The interaction of the various mucosal protective components helps maintain structural and functional homeostasis. There is increasing evidence suggesting that the upper GI microbiota plays a crucial role in the defense mechanisms. However, this warrants further investigation.

The Rise of Colorectal Cancer in Asia: Epidemiology, Screening, and Management Abstract Purpose of Review Colorectal cancer (CRC) remains the third most commonly diagnosed cancer globally, and its incidence and mortality rates have been on the rise in Asia. In this paper, we summarize the recent trends and screening challenges of CRC in this region. Recent Findings In 2018, Asia had the highest proportions of both incident (51.8%) and mortality (52.4%) CRC cases (all genders and ages) per 100,000 population in the world. In addition, there has been a rising trend of this disease across Asia with some regional geographic variations. This rise in CRC can be attributed to westernized dietary lifestyle, increasing population aging, smoking, physical inactivity, and other risk factors. In curbing the rising trend, Japan, South Korea, Singapore, and Taiwan have launched nationwide population-based screening programs. CRC screening across this region has been found to be effective and cost-effective compared with no screening at all. The emergence of new therapies has caused a reduction in case fatality; however, these new options have had a limited impact on cure rates and long-term survival due to the great disparity in treatment capacity/resources and screening infrastructures among Asian countries with different degrees of economic development. Summary CRC is still rising in Asia, and implementation of screening is necessary for moderate- to high-incidence countries and construction of treatment capacity is the priority task in low-incidence and low-income countries. Unless countries in Asia implement CRC screening, the incidence and mortality rates of this disease will continue to rise especially with the rapidly rising population growth, economic development, westernized lifestyle, and increasing aging.

Nutrition in Cirrhosis Abstract Purpose of Review This review discusses the prevalence of malnutrition in cirrhosis, metabolic functions of the liver and alterations in cirrhosis, malnutrition screening tools, and common macronutrient and micronutrient deficiencies encountered in individuals with chronic liver disease and their impact on morbidity and mortality. Recent Findings Several meta-analyses and international society guidelines recommend malnutrition screening and nutrition interventions to improve outcomes in all patients with chronic liver disease given their high risk of malnutrition which is often under recognized. Summary Malnutrition is common in individuals with chronic liver disease and has a significant impact on patient outcomes. Thus, it is critical that validated malnutrition screening tools are used routinely in this patient population in order to identify high-risk patients and implement nutrition and exercise interventions early.

Popular Remedies for Esophageal Symptoms: a Critical Appraisal Abstract Purpose of Review Popular remedies are of ongoing interest to patients experiencing common esophageal symptoms, particularly as typical pharmacologic interventions have been subject to increased scrutiny. Herein we summarize the available data regarding potential risks and benefits of several such remedies. Recent Findings With emphasis on reflux and non-cardiac chest pain, research is ongoing into the clinical utility and diverse physiologic mechanisms underlying a variety of complementary and alternative modalities, including dietary manipulation, apple cider vinegar, melatonin, acupuncture, and various herbal products (rikkunshito, STW 5, slippery elm, licorice, and peppermint oil, among others). Summary A substantial gap persists between anecdotal and empirical understandings of the majority of non-pharmacologic remedies for esophageal symptoms. This landscape of popular treatments nevertheless raises several interesting mechanistic hypotheses and compelling opportunities for future research.

Colonic and Anorectal Manifestations of Systemic Sclerosis Abstract Purpose of Review Systemic sclerosis is a chronic autoimmune disorder commonly involving the gastrointestinal tract, including the colon and anorectum. In this review, we summarize major clinical manifestations and highlight recent developments in physiology, diagnostics, and treatment. Recent Findings The exact pathophysiology of systemic sclerosis is unclear and likely multifactorial. The role of the microbiome on gastrointestinal manifestations has led to a better understanding of potential pathogenic gut flora. Carbohydrate malabsorption is common. Evaluation using fecal calprotectin and high-resolution anorectal manometry may broaden our understanding of the etiologies of diarrhea and fecal incontinence and help with early recognition of pathology. Prucalopride, a high-affinity 5HT4 agonist, and pyridostigmine, an acetylcholinesterase inhibitor, may help improve colonic transit in patients with constipation. Intravenous immunoglobulins have been used to target muscarinic receptor antibodies that are believed to contribute to gastrointestinal dysmotility. Summary Colonic and anorectal manifestations of systemic sclerosis include constipation, diarrhea, and fecal incontinence, and can diminish quality of life for these patients. Recent studies regarding pathophysiology as well as diagnostic and treatment options are promising. Further targeted studies to facilitate early intervention and better management of refractory symptoms are still needed.

Evaluation and Management of Cirrhotic Patients Undergoing Elective Surgery Abstract Purpose of Review Cirrhotic patients have an increased risk of surgical complications and higher perioperative morbidity and mortality based on the severity of their liver disease. Liver disease predisposes patients to perioperative coagulopathies, volume overload, and encephalopathy. The goal of this paper is to discuss the surgical risk of cirrhotic patients undergoing elective surgeries and to discuss perioperative optimization strategies. Recent Findings Literature thus far varies by surgery type and the magnitude of surgical risk. CTP and MELD classification scores allow for the assessment of surgical risk in cirrhotic patients. Summary Once the decision has been made to undergo elective surgery, cirrhotic patients can be optimized pre-procedure with the help of a checklist and by the involvement of a multidisciplinary team. Elective surgeries should be performed at hospital centers staffed by healthcare providers experienced in caring for cirrhotic patients. Further research is needed to develop ways to prepare this complicated patient population before elective surgery.

The Status of SEMS Versus Plastic Stents for Benign Biliary Strictures Abstract Purpose of Review Benign biliary strictures can be treated with plastic stents and self-expandable metal stents (SEMS). This review article delineates the latest scientific evidence for their usage. Recent Findings Despite evolving literature on both type of stents as treatment modalities of benign biliary strictures, which encompass mainly anastomotic strictures and strictures related to chronic pancreatitis, no final conclusions can be drawn regarding the superiority of a particular stent. SEMS tend to have higher stricture resolution rates and fewer procedural requirements which are partly offset by higher stent migration and stricture recurrence rates compared with plastic stents. Summary Additional studies focusing on new SEMS types with anti-migration features as well as cost-effectiveness calculations are necessary for clinical decision-making when treating patients with benign biliary strictures.

Clinical Aspects of Thickeners for Pediatric Gastroesophageal Reflux and Oropharyngeal Dysphagia Abstract Purpose of Review The purpose of this review is to discuss current knowledge and recent findings regarding clinical aspects of thickeners for pediatric gastroesophageal reflux and oropharyngeal dysphagia. We review evidence for thickener efficacy, discuss types of thickeners, practical considerations when using various thickeners, and risks and benefits of thickener use in pediatrics. Recent Findings Thickeners are effective in decreasing regurgitation and improving swallowing mechanics and can often be used empirically for the treatment of infants and young children. Adverse effects have been reported, but with careful consideration of appropriate thickener types, desired thickening consistency, and follow-up in collaboration with feeding specialists, most patients have symptomatic improvements. Summary Thickeners are typically well tolerated and with few side effects, but close follow-up is needed to make sure patients tolerate thickeners and have adequate symptom improvement.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Lipidology

Editorial introduction No abstract available

Non-HDL cholesterol should not generally replace LDL cholesterol in the management of hyperlipidaemia Purpose of review Non-HDL cholesterol was originally conceived as a therapeutic target for statin treatment in hypertriglyceridaemia when apolipoprotein B100 assays were not widely available. Recently non-HDL cholesterol has been recommended to replace LDL cholesterol in the clinical management of dyslipidaemia routinely in general medical practice. This is misguided. Recent findings Non-HDL cholesterol is heterogeneous, constituting a mixture of triglyceride-rich VLDL, intermediate density lipoprotein and LDL in which small dense LDL is poorly represented and to which VLDL cholesterol contributes increasingly as triglyceride levels rise. This makes it unsuitable as a goal of lipid-lowering treatment or as an arbiter of who should receive such treatment. Results of trials designed to lower LDL cholesterol are not easily translated to non-HDL cholesterol. Fasting is no longer thought essential for screening the general population for raised LDL cholesterol. ApoB100 measurement also does not require fasting even in rarer more extreme lipoprotein disorders encountered in the Lipid Clinic, provides greater precision and specificity and overcomes the problems posed by LDL and non-HDL cholesterol. It is more easily interpreted both in diagnosis and as a therapeutic goal and it includes SD-LDL. Summary If we are to discourage use of LDL cholesterol, it should be in favour of apoB100 not non-HDL cholesterol.

Update on low-density lipoprotein cholesterol quantification Purpose of review β-Quantification is considered the reference measurement procedure for low-density lipoprotein cholesterol (LDL-C). However, this technique is time-consuming and thus is inappropriate for routine clinical practice. Therefore, the Friedewald equation or homogeneous assays have been widely utilized. As several pitfalls exist with these two methods, a novel method for estimating LDL-C was developed by Martin et al. Recent findings Martin's method uses a strata-specific median for the triglycerides/very low-density lipoprotein cholesterol (VLDL-C) ratio on the basis of triglycerides and non-HDL-C concentrations. Recent studies show that Martin's method better correlates with β-quantification or homogeneous assays compared with the Friedewald equation, especially with values of triglycerides at least 150 mg/dl and/or LDL-CD less than 70 mg/dl. Such findings have also been demonstrated in other ethnic groups (Japanese and Korean) and disease populations, including diabetes and cardiovascular disease, in which the triglycerides/VLDL-C ratio can be affected. Summary For the current therapeutic goal of LDL-C values below 70 mg/dl in high-risk patients, accurate assessment of LDL-C levels at very low levels is required. Martin's method could overcome pitfalls such as underestimation of the Friedewald equation at this level. Further evaluation of the triglycerides/VLDL-C ratio in participants with diverse ethnic backgrounds or clinical conditions would expand the implementation of this novel method.

Recent developments in lipodystrophy Purpose of review Lipodystrophy syndromes have an estimated prevalence of 1.3–4.7 cases per million and as with other rare diseases conducting research can be challenging. The present review highlights recently published work that has provided insights into the field of non-HIV--associated lipodystrophy syndromes. Recent findings Lipodystrophies are a heterogenous group of disorders, as such research is often focused on specific subtypes of the condition. The identification of children carrying LMNA mutations has provided insights into the natural history of FPLD2, specifically that the adipose tissue phenotype predates the onset of puberty. Recent reports of PLIN1 heterozygous null variant carriers and the apparent absence of a lipodystrophy phenotype challenges our understanding of the molecular biology of perilipin 1 and its role in the pathogenesis of FPLD4. With a focus on therapeutics, studies delineating the differential responsiveness of PPARγ mutants to endogenous and synthetic ligands has illustrated the potential for pharmacogenetics to inform therapeutic decisions in lipodystrophy related to PPARG mutations, whereas robust human studies have provided insight into the food independent metabolic effects of leptin in lipodystrophy. Finally, rare syndromes of lipodystrophy continue to serve as an exemplar for the contribution of genetically determined adipose tissue expandability to metabolic disease in the general population. Summary Lipodystrophy research continues to illuminate our understanding of this rare disease and the possibility that lipodystrophy syndromes and the metabolic syndrome may have shared pathophysiology.

Is hypertriglyceridemia atherogenic? Purpose of review Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as 'bystanders' for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases. Recent findings The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death. Summary For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.

Monogenic, polygenic, and oligogenic familial hypercholesterolemia Purpose of review Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease. Recent findings Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia. Summary Familial hypercholesterolemia is a relatively common 'genetic' disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.

Inheritance of high and low HDL: mechanisms and management Purpose of review The inverse association between plasma high-density lipoprotein cholesterol (HDL-C) concentration and the incidence of cardiovascular disease (CVD) has been unequivocally proven by many epidemiological studies. There are several genetic disorders affecting HDL-C plasma levels, either providing atheroprotection or predisposing to premature atherosclerosis. However, up to date, there has not been any pharmacological intervention modulating HDL-C levels, which has been clearly shown to prevent the progression of CVD. Thus, clarifying the exact underlying mechanisms of inheritance of these genetic disorders that affect HDL is a current goal of the research, as key roles of molecular components of HDL metabolism and function can be revealed and become targets for the discovery of novel medications for the prevention and treatment of CVD. Recent findings Primary genetic disorders of HDL can be either associated with longevity or, in contrast, may lead to premature CVD, causing high morbidity and mortality to their carriers. A large body of recent research has closely examined the genetic disorders of HDL and new promising therapeutic strategies have been developed, which may be proven beneficial in patients predisposed to CVD in the near future. Summary We have reviewed recent findings on the inheritance of genetic disorders associated with high and low HDL-C plasma levels and we have discussed their clinical features, as well as information about new promising HDL-C-targeted therapies that are under clinical trials.

High-density lipoprotein: our elusive friend Purpose of review Despite advances in the research on HDL composition (lipidomics and proteomics) and functions (cholesterol efflux and antioxidative capacities), the relationship between HDL compositional and functional properties is not fully understood. We have reviewed the recent literature on this topic and pointed out the difficulties which limit our understanding of HDL's role in cardiovascular disease (CVD). Recent findings Though current findings strongly support that HDL has a significant role in CVD, the underlying mechanisms by which HDL mitigates CVD risk are not clear. This review focuses on studies that investigate the cell-cholesterol efflux capacity and the proteomic and lipidomic characterization of HDL and its subfractions especially those that analyzed the relationship between HDL composition and functions. Summary Recent studies on HDL composition and HDL functions have greatly contributed to our understanding of HDL's role in CVD. A major problem in HDL research is the lack of standardization of both the HDL isolation and HDL functionality methods. Data generated by different methods often produce discordant results on the particle number, size, lipid and protein composition, and the various functions of HDL.

Role of serum amyloid A in atherosclerosis Purpose of review Acute phase serum amyloid A (SAA) is persistently elevated in chronic inflammatory conditions, and elevated levels predict cardiovascular risk in humans. More recently, murine studies have demonstrated that over-expression of SAA increases and deficiency/suppression of SAA attenuates atherosclerosis. Thus, beyond being a biomarker, SAA appears to play a causal role in atherogenesis. The purpose of this review is to summarize the data supporting SAA as a key player in atherosclerosis development. Recent findings A number of pro-inflammatory and pro-atherogenic activities have been ascribed to SAA. However, the literature is conflicted, as recombinant SAA, and/or lipid-free SAA, used in many of the earlier studies, do not reflect the activity of native human or murine SAA, which exists largely lipid-associated. Recent literatures demonstrate that SAA activates the NLRP3 inflammasome, alters vascular function, affects HDL function, and increases thrombosis. Importantly, SAA activity appears to be regulated by its lipid association, and HDL may serve to sequester and limit SAA activity. Summary SAA has many pro-inflammatory and pro-atherogenic activities, is clearly demonstrated to affect atherosclerosis development, and may be a candidate target for clinical trials in cardiovascular diseases.

The future of apolipoprotein E mimetic peptides in the prevention of cardiovascular disease Purpose of review This review aims to discuss the recent developments in the area of apolipoprotein E (apoE) mimetics and their therapeutic potential for treating cardiovascular disease, the leading cause of mortality worldwide. Recent findings Ongoing research efforts target the development of novel therapies that would not only reduce circulating levels of atherogenic lipoproteins, but could also increase high density lipoprotein cholesterol (HDL-C) levels and/or improve HDL function. Among them, synthetic peptides that mimic the structure of natural human apoE, a component of triglyceride-rich lipoproteins and HDL, have been designed and proven to be functionally similar to apoE. In specific, apoE mimetic peptides mediate hepatic clearance of circulating atherogenic lipoproteins, dramatically reduce plasma cholesterol, and lead to attenuation of atherosclerosis development in vivo. These peptides also exhibit pleiotropic antiatherogenic properties, such as macrophage cholesterol efflux capacity, as well as anti-inflammatory and antioxidative functions. Summary ApoE mimetics are undergoing preclinical and clinical evaluation with promising results to date that render them attractive candidates in cardiovascular disease prevention and treatment.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Sexually Transmitted Diseases

The National Network of Sexually Transmitted Disease Clinical Prevention Training Centers Turns 40—A Look Back, a Look Ahead Since 1979, the National Network of Sexually Transmitted Disease (STD) Clinical Prevention Training Centers (NNPTC) has provided state-of-the-art clinical and laboratory training for STD prevention across the United States. This article provides an overview of the history and activities of the NNPTC from its inception to present day, and emphasizes the important role the network continues to play in maintaining a high-quality STD clinical workforce. Over time, the NNPTC has responded to changing STD epidemiological patterns, technological advances, and increasing private-sector care-seeking for STDs. Its current structure of integrated regional and national training centers allows NNPTC members to provide dynamic, tailored responses to STD training needs across the country.

Sexually Transmitted Disease Partner Services Costs, Other Resources, and Strategies Across Jurisdictions to Address Unique Epidemic Characteristics and Increased Incidence Background Sexually transmitted disease (STD) partner services (PS) are a core component of STD programs. Data on costs are needed to support PS programming. Methods In Washington State STD PS programs, disease intervention specialists (DIS) conduct telephone-based interviews and occasional field visits, offer expedited partner therapy to heterosexuals with gonorrhea or chlamydia, and promote human immunodeficiency virus (HIV) testing, preexposure prophylaxis, and HIV care. We conducted activity-based microcosting of PS, including: observational and self-reported time studies and interviews. We analyzed cost, surveillance, and service delivery data to determine costs per program outcomes. Results In King, Pierce, and Spokane counties, respectively, DIS allocated 6.5, 6.4, and 28.8 hours per syphilis case and 1.5, 1.6, and 2.9 hours per gonorrhea/chlamydia case, on average. In 2016, each full-time DIS investigated 270, 268, and 61 syphilis and 1177, 1105, and 769 gonorrhea/chlamydia cases. Greater than 80% of syphilis cases in King and Pierce were among men who have sex with men versus 38% in Spokane. Disease intervention specialists spent 12% to 39% of their time actively interviewing cases and notifying partners (clients), and the remaining time locating clients, coordinating and verifying care, and managing case reports. Time spent on expedited partner therapy, HIV testing, and referrals to HIV treatment or preexposure prophylaxis, was minimal (<5 minutes per interview) at locations with resources outside PS staff. Program cost-per-interview ranged from US $527 to US $2210 for syphilis, US $219 to US $484 for gonorrhea, and US $164 to US $547 for chlamydia. Discussion The STD PS resource needs depended on epidemic characteristics and program models. Integrating HIV prevention objectives minimally impacted PS-specific program costs. Results can inform program planning, future budget impact, and cost-effectiveness analyses.

Changes in Patient Visits After the Implementation of Insurance Billing at a Sexually Transmitted Diseases Clinic in a Medicaid Expansion State Background Medicaid expansion has led to unique opportunities for sexually transmitted disease (STD) clinics to improve the sustainability of services by billing insurance. We evaluated changes in patient visits after the implementation of insurance billing at a STD clinic in a Medicaid expansion state. Methods The Rhode Island STD Clinic offered HIV/STD screening services at no cost to patients until October 2016, when insurance billing was implemented. Care for uninsured patients was still provided for free. We compared the clinic visits in the preinsurance period with the postinsurance period using t-tests, Poisson regressions, and a logistic regression. Results A total of 5560 patients were seen during the preinsurance (n = 2555) and postinsurance (n = 3005) periods. Compared with the preinsurance period, the postinsurance period had a significantly higher average number of patient visits/month (212.9 vs. 250.4, P = 0.0016), including among patients who were black (36.8 vs. 50.3, P = 0.0029), Hispanic/Latino (50.8 vs. 65.8, P = 0.0018), and insured (106.3 vs. 130.1, P = 0.0025). The growth rate of uninsured (+0.10 vs. +4.11, P = 0.0026) and new patients (−4.28 vs. +1.07, P = 0.0007) also increased between the two periods. New patients whose first visit was before the billing change had greater odds (adjusted odds ratio, 2.68, 95% confidence interval, 2.09–3.44; P < 0.0001) of returning compared with new patients whose first visit was after the billing change. Conclusions Implementation of insurance billing at a publicly funded STD clinic, with free services provided to uninsured individuals, was associated with a modest increase in patient visits and a decline in patients returning for second visits.

Iowa TelePrEP: A Public-Health-Partnered Telehealth Model for Human Immunodeficiency Virus Preexposure Prophylaxis Delivery in a Rural State Background Access to human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is often poor in small urban and rural areas because of stigma and long distances to providers. The Iowa Department of Public Health and The University of Iowa created a regional telehealth program to address these barriers ("Iowa TelePrEP"). We describe initial TelePrEP results and share lessons learned. Methods Iowa Department of Public Health personnel in sexually transmitted infection (STI) clinics, disease intervention specialist and partner services, and HIV testing programs referred clients to pharmacists at University of Iowa. Clients could also self-refer via a website. Pharmacists completed video visits with clients in the community on smartphones and other devices, arranged local laboratory studies, and mailed medications. We performed a retrospective record review to quantify rates of PrEP referral, initiation, retention, guideline-concordant laboratory monitoring, and STI identification and treatment. Results Between February 2017 and October 2018, TelePrEP received 186 referrals (37% from public health) and completed 127 (68%) initial video visits with clients. Median client age was 32; 91% were men who have sex with men. Most clients with video visits (91%) started PrEP. Retention in TelePrEP at 6 months was 61%, and 96% of indicated laboratory monitoring tests were completed. Screening identified 37 STIs (8 syphilis, 10 gonorrhea, 19 chlamydia). Disease intervention specialist and partner services linked all clients with STIs to local treatment within 14 days (80% in 3 days). Conclusions Using widely available technology and infrastructure, public health departments and health care systems can collaborate to develop regional telehealth programs to deliver PrEP in small urban and rural settings.

Men Who Have Sex With Men With Mycoplasma genitalium–Positive Nongonococcal Urethritis Are More Likely to Have Macrolide-Resistant Strains Than Men With Only Female Partners: A Prospective Study Background Mycoplasma genitalium was previously less common among men who have sex with men (MSM) compared with men with only female partners (MSW) in men with nongonococcal urethritis (NGU) in Sydney, Australia. We aimed to determine the prevalence of M. genitalium and of macrolide-resistant M. genitalium in men with NGU and to compare differences between prevalence and resistance rates between MSM and MSW. Methods We enrolled 588 men with NGU in a prospective study at two urban sexual health services. The ResistancePlus MG assay (SpeeDx, Australia) was used to detect both M. genitalium, and macrolide resistance-associated mutations in first-void urine samples. Demographic, behavioral and clinical data were analyzed to investigate associations with M. genitalium infection or the presence of macrolide resistance. Results Mycoplasma genitalium prevalence was 12.8% (75 of 588) overall and among MSM (12.8% [39 of 306]) and MSW (12.8% [36 of 282]; risk ratio [RR], 1.00; 95% confidence interval [CI], 0.65–1.52). Overall, 70.7% (53 of 75) of M. genitalium strains were macrolide-resistant, with significantly more resistance among MSM (89.7%, 35 of 39) than MSW (50%, 18 of 36) (RR, 1.80; 95% CI, 1.27–2.54; P = 0.001). On multivariate analysis, the presence of M. genitalium macrolide resistance mutations was independently associated with having male sexual partners compared with having only female partners (RR, 1.55; 95% CI, 1.02–2.38; P = 0.042). Conclusions Prevalence of M. genitalium among men with NGU is now similar for MSW and MSM and has increased locally from 5.2% to 12.8% within the last 10 years. Men who have sex with men are significantly more likely than MSW to harbor macrolide-resistant M. genitalium infections. This has treatment implications.

Mycoplasma genitalium Nongonococcal Urethritis Is Likely to Increase in Men Who Have Sex With Men Who Practice Unsafe Sex: What Should We Do? No abstract available

Factors Associated With Increased Syphilis Screening Among People Living With Human Immunodeficiency Virus Background Antiretroviral therapy effectively reduces the risk of human immunodeficiency virus transmission, but in the context of undetectable equals untransmittable and decreased condom use, rates of syphilis are increasing. In Oregon, syphilis has risen over 20-fold in the past decade, from less than 30 to approximately 600 cases annually during 2016 and 2017. Although many cases are among people living with human immunodeficiency virus infection (PLWH), screening for syphilis among PLWH is often lacking. The objective of this study was to estimate the prevalence of past-year syphilis testing among PLWH in Oregon to identify facility-level and individual-level factors associated with testing. Methods We examined 2015 to 2016 Medical Monitoring Project interview and medical records data in Oregon and conducted supplemental interviews with participants' medical providers. We used generalized mixed effects models to identify factors associated with syphilis screening. Results Sixty-nine percent of Medical Monitoring Project participants had past-year syphilis screening. Patients receiving care from facilities with written sexually transmitted infection screening policies were far more likely to be screened than those receiving care from facilities without written policies (94% vs. 43%, P < 0.001). Participants who identified as male were more likely to have been tested, even after adjusting for facility-level characteristics. Clustering within facility accounted for about 15% of the unexplained variability in the adjusted mixed effects models. Conclusions Written sexually transmitted infection screening policies at medical facilities appear to be an important tool for ensuring syphilis screening occurs as recommended to prevent the continued rise in syphilis.

Excess Cancer Cases and Medical Costs Due to Suboptimal Human Papillomavirus Vaccination Coverage in California Background Human papillomavirus (HPV) vaccination coverage continues to be at low to moderate levels throughout the United States. HPV infection is linked to multiple types of cancers resulting in high economic and health burden. We aimed to estimate the excess number of cancer cases and associated medical costs due to current HPV vaccination coverage for a 20-year-old birth cohort in California. Methods We estimated the lifetime number of cancer cases caused by vaccine-preventable strains of HPV for a cohort of 20 year-olds in California. We then estimated the excess number of cancer cases in that cohort which would occur due to 2017 HPV vaccination coverage compared with an optimal coverage of 99.5%. By multiplying those excess cases by the average cost of treatment, we determined the excess cost due to current HPV vaccination coverage. Results With current vaccination coverage in California, the 20-year-old cohort is at risk for an excess 1352 cancer cases that could be prevented with a projected optimal vaccination coverage of 99.5%. The excess cost of treatment for those cancer cases would be US $52.2 million. Male oropharyngeal cancer accounts for the greatest projected cost burden US $21.3 million followed by cervical cancer US $16.1 million. Conclusions Increased HPV vaccination coverage in California is needed to reduce economic and health burdens associated with cancers caused by HPV infection.

Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya Background Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes. Methods This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks. Results In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P = 0.044). Conclusions High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China Background World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. Methods We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. Results CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. Conclusions When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com