Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated ...comprehensively, because available studies have involved limited genomic scope and limited sample sizes.
This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.
Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank.
The hazard ratio (HR) for CAD was 1.71 (95% confidence interval CI: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age.
The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.
This paper describes characteristics of opioid use episodes for noncancer pain and defines thresholds for de facto long-term opioid therapy.
CONSORT (CONsortium to Study Opioid Risks and Trends) ...includes adult members of 2 health plans serving over 1% of the US population. Opioid use episodes beginning in the years 1997 to 2005 were classified as acute, episodic, long-term/lower dose, or long-term/higher dose.
On the basis of evaluation of the likelihood of opioid use continuing, long-term opioid therapy was defined by episodes lasting longer than 90 days with 10+ opioid prescriptions or 120+ days supply of opioids dispensed. Long-term/higher dose episodes (<1.5% of all opioid use episodes) were characterized by daily or near daily use, a mean duration of about 1000 days, and an average daily dose of about 55 mg. They accounted for more than half the total morphine equivalents dispensed from the years 1997 to 2006. Short-acting, non-Schedule II opioids (eg, hydrocodone with acetaminophen) were, by far, the most commonly prescribed medications for acute, episodic, and long-term episodes. Long-acting (sustained-release) opioids were the predominately prescribed medication in a minority of long-term episodes (6% to 12%).
Long-term opioid therapy was characterized by the diversity in medications prescribed, dosage levels, and frequency of use. The proposed threshold for long-term opioid therapy provides a checkpoint for physicians to review whether an explicit decision to sustain opioid therapy has been reached, and to ensure that a documented treatment plan and provisions for monitoring medication use and patient outcomes are in place.
Colonoscopy is a widely performed procedure with procedural volumes increasing annually throughout the world. Many procedures are now performed as part of colorectal cancer screening programmes. ...Colonoscopy should be of high quality and measures of this quality should be evidence based. New UK key performance indicators and quality assurance standards have been developed by a working group with consensus agreement on each standard reached. This paper reviews the scientific basis for each of the quality measures published in the UK standards.
Long-term opioid therapy for chronic noncancer pain is becoming increasingly common in community practice. Concomitant with this change in practice, rates of fatal opioid overdose have increased. The ...extent to which overdose risks are elevated among patients receiving medically prescribed long-term opioid therapy is unknown.
To estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy.
Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at the time of overdose.
HMO.
9940 persons who received 3 or more opioid prescriptions within 90 days for chronic noncancer pain between 1997 and 2005.
Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes--nonfatal and fatal overdoses--were identified through diagnostic codes from inpatient and outpatient care and death certificates and were confirmed by medical record review.
51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate.
Increased overdose risk among patients receiving higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation.
Patients receiving higher doses of prescribed opioids are at increased risk for overdose, which underscores the need for close supervision of these patients.
National Institute of Drug Abuse.
Acquired tracheal stenosis can result from iatrogenic injury or, less commonly, tracheal tumors. Symptoms can arise insidiously and typically include respiratory distress, sleep disordered breathing, ...or exercise intolerance. Diagnostic evaluation includes cross-sectional imaging and endoscopy. Various endoscopic and open procedures exist to address acquired tracheal stenosis and treatment should be tailored to the patient. Cervical slide tracheoplasty without cardiopulmonary bypass is a versatile technique that can address different types of tracheal stenosis. It allows for immediate reconstruction with vascularized tissue and continued opportunity for growth as the child ages, with high success rates with minimal morbidity.
Subglottic stenosis Jefferson, Niall D., MD, FRACS; Cohen, Aliza P., MA; Rutter, Michael J., MBChB, FRACS
Seminars in pediatric surgery,
06/2016, Letnik:
25, Številka:
3
Journal Article
Recenzirano
Subglottic stenosis (SGS) is a congenital or acquired condition characterized by a narrowing of the upper airway extending from just below the vocal folds to the lower border of the cricoid ...cartilage. With the introduction of prolonged intubation in neonates (mid 1960s), acquired SGS became the most frequent cause of laryngeal stenosis; unlike congenital SGS, it does not improve with time. Laryngeal reconstruction surgery evolved as a consequence of the need to manage these otherwise healthy but tracheotomized children. Ongoing innovations in neonatal care have gradually led to the salvage of premature and medically fragile infants in whom laryngeal pathology is often more severe, and in whom stenosis often involves not only the subglottis, but also the supraglottis or glottis—causing significant morbidity and mortality. The primary objective of intervention in these children is decannulation or preventing the need for tracheotomy. The aim of this chapter is to present a more detailed description of both congenital and acquired SGS, highlighting the essentials of diagnostic assessment and familiarizing the reader with contemporary management approaches.
Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published ...technical standards on how to perform FAE in children are lacking.
The American Thoracic Society (ATS) approved the formation of a multidisciplinary committee to delineate technical standards for performing FAE in children. The committee completed a pragmatic synthesis of the evidence and used the evidence synthesis to answer clinically relevant questions.
There is a paucity of randomized controlled trials in pediatric FAE. The committee developed recommendations based predominantly on the collective clinical experience of our committee members highlighting the importance of FAE-specific airway management techniques and anesthesia, establishing suggested competencies for the bronchoscopist in training, and defining areas deserving further investigation.
These ATS-sponsored technical standards describe the equipment, personnel, competencies, and special procedures associated with FAE in children.
Context:
Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol ...(E2) may also be associated with MetS, but few studies have investigated this.
Objective:
To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk.
Methods:
Three thousand three hundred sixty nine community-dwelling men aged 40–79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS.
Results:
One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P = .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001).
Conclusions:
In men, lower T levels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
Objectives/Hypothesis
Children with bilateral true vocal fold immobility (BTVFI) may present with significant airway distress necessitating tracheostomy. The objective of this study was to review our ...preliminary experience with the anterior–posterior cricoid split (APCS), an endoscopic intervention used as an alternative to tracheostomy in children with BTVFI.
Study Design
Multicenter review.
Methods
A review of patients undergoing endoscopic APCS for BTVFI at four institutions was performed. Patients were evaluated for the ability to ventilate without the requirement for tracheostomy or reintubation. Additional data extracted included the duration of intubation following APCS, the requirement for additional procedures, and demographics. Surgical success was defined as the ability to avoid tracheostomy and to cap or decannulate without respiratory symptoms if a tracheostomy was present prior to APCS.
Results
Nineteen APCS procedures were performed between October 2010 and June 2016. There were 12 male patients, the mean age at APCS was 4.7 months. BTVFI was primarily idiopathic (58%) and associated with other comorbidities (74%). All patients were candidates for tracheostomy prior to APCS. Fourteen patients (74%) were considered surgical successes. Of the unsuccessful patients, three (66%) required tracheostomy following APCS, and one was treated with a posterior cartilage graft. There was one nonsurgical mortality greater than 2 months after APCS and thought to be unrelated to the airway.
Conclusions
Endoscopic APCS appears to be a safe and effective intervention for pediatric BTVFI. Under the correct circumstances, this can be performed as a single procedure, obviating tracheostomy. Further study is warranted.
Level of Evidence
4. Laryngoscope, 128:257–263, 2018
PDF
