Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea

Background: In 2015, a large outbreak of Middle East respiratory syndrome (MERS) occurred in the Republic of Korea. Half of the cases were associated with a tertiary care university hospital. Objective: To document the outbreak and successful control measures. Design: Descriptive study. Setting: A 1950-bed tertiary care university hospital. Patients: 92 patients with laboratory-confirmed MERS and 9793 exposed persons. Measurements: Description of the outbreak, including a timeline, and evaluation of the effectiveness of the control measures. Results: During the outbreak, 92 laboratory-confirmed MERS cases were associated with a large tertiary care hospital, 82 of which originated from unprotected exposure to 1 secondary patient. Contact tracing and monitoring exposed patients and assigned health care workers were at the core of the control measures in the outbreak. Nontargeted screening measures, including body temperature screening among employees and visitors at hospital gates, monitoring patients for MERS-related symptoms, chest radiographic screening, and employee symptom monitoring, did not detect additional patients with MERS without existing transmission links. All in-hospital transmissions originated from 3 patients with MERS who also had pneumonia and productive cough. Limitations: This was a retrospective single-center study. Statistical analysis could not be done. Because this MERS outbreak originated from a superspreader, effective control measures could differ in endemic areas or in other settings. Conclusion: Control strategies for MERS outbreaks should focus on tracing contacts of persons with epidemiologic links. Adjusting levels of quarantine and personal protective equipment according to the assumed infectivity of each patient with MERS may be appropriate. Primary Funding Source: Samsung Biomedical Research Institute.

Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma

Background: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. Purpose: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. Data Sources: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. Study Selection: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. Data Extraction: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. Data Synthesis: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: β-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). Limitation: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. Conclusion: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis. Primary Funding Source: National Eye Institute, National Institutes of Health.

Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force

Background: Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. Purpose: To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. Data Sources: Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. Study Selection: Trials and recent systematic reviews of treatment, test–retest studies of screening, and trials and large cohort studies for harms. Data Extraction: Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. Data Synthesis: Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. Limitation: The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. Conclusion: No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. Primary Funding Source: Agency for Healthcare Research and Quality.

Prognostic Value of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Suspected Coronary Heart Disease: Long-Term Follow-up of a Prospective, Diagnostic Accuracy Cohort Study

Background: There are no prospective, prognostic data comparing cardiovascular magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) in the same population of patients with suspected coronary heart disease (CHD). Objective: To establish the ability of CMR and SPECT to predict major adverse cardiovascular events (MACEs). Design: Annual follow-up of the CE-MARC (Clinical Evaluation of MAgnetic Resonance imaging in Coronary heart disease) study for a minimum of 5 years for MACEs (cardiovascular death, acute coronary syndrome, unscheduled revascularization or hospital admission for cardiovascular cause). (Current Controlled Trials registration: ISRCTN77246133) Setting: Secondary and tertiary care cardiology services. Participants: 752 patients from the CE-MARC study who were being investigated for suspected CHD. Measurements: Prediction of time to MACE was assessed by using univariable (log-rank test) and multivariable (Cox proportional hazards regression) analysis. Results: 744 (99%) of the 752 recruited patients had complete follow-up. Of 628 who underwent CMR, SPECT, and the reference standard test of X-ray angiography, 104 (16.6%) had at least 1 MACE. Abnormal findings on CMR (hazard ratio, 2.77 [95% CI, 1.85 to 4.16]; P < 0.001) and SPECT (hazard ratio, 1.62 [CI, 1.11 to 2.38; P = 0.014) were both strong and independent predictors of MACE. Only CMR remained a significant predictor after adjustment for other cardiovascular risk factors, angiography result, or stratification for initial patient treatment. Limitation: Data are from a single-center observational study (albeit conducted in a high-volume institution for both CMR and SPECT). Conclusion: Five-year follow-up of the CE-MARC study indicates that compared with SPECT, CMR is a stronger predictor of risk for MACEs, independent of cardiovascular risk factors, angiography result, or initial patient treatment. This further supports the role of CMR as an alternative to SPECT for the diagnosis and management of patients with suspected CHD. Primary Funding Source: British Heart Foundation.

Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 164, No 6

Background: Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN). Purpose: To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures. Data Sources: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015. Study Selection: Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging. Data Extraction: Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results. Data Synthesis: None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk. Limitations: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment. Conclusion: No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance. Primary Funding Source: Agency for Healthcare Research and Quality.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study: Annals of Internal Medicine: Vol 164, No 11

Background: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. Objective: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. Design: Retrospective cohort study. Setting: An integrated health care delivery system. Participants: All enrollees with biochemically confirmed PHPT from 1995 to 2010. Measurements: Bone mineral density (BMD) changes and fracture rate. Results: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (−6.6% and −7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. Limitation: Retrospective study design and nonrandom treatment assignment. Conclusion: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. Primary Funding Source: National Institute on Aging.

Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality: A Cohort Study: Annals of Internal Medicine: Vol 164, No 8

Background: Prior mortality studies have concluded that elevated body mass index (BMI) may improve survival. These studies were limited because they did not measure adiposity directly. Objective: To examine associations of BMI and body fat percentage (separately and together) with mortality. Design: Observational study. Setting: Manitoba, Canada. Participants: Adults aged 40 years or older referred for bone mineral density (BMD) testing. Measurements: Participants had dual-energy x-ray absorptiometry (DXA), entered a clinical BMD registry, and were followed using linked administrative databases. Adjusted, sex-stratified Cox models were constructed. Body mass index and DXA-derived body fat percentage were divided into quintiles, with quintile 1 as the lowest, quintile 5 as the highest, and quintile 3 as the reference. Results: The final cohort included 49 476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%). Death occurred in 4965 women over a median of 6.7 years and 984 men over a median of 4.5 years. In fully adjusted mortality models containing both BMI and body fat percentage, low BMI (hazard ratio [HR], 1.44 [95% CI, 1.30 to 1.59] for quintile 1 and 1.12 [CI, 1.02 to 1.23] for quintile 2) and high body fat percentage (HR, 1.19 [CI, 1.08 to 1.32] for quintile 5) were associated with higher mortality in women. In men, low BMI (HR, 1.45 [CI, 1.17 to 1.79] for quintile 1) and high body fat percentage (HR, 1.59 [CI, 1.28 to 1.96] for quintile 5) were associated with increased mortality. Limitations: All participants were referred for BMD testing, which may limit generalizability. Serial measures of BMD and weight were not used. Some measures, such as physical activity and smoking, were unavailable. Conclusion: Low BMI and high body fat percentage are independently associated with increased mortality. These findings may help explain the counterintuitive relationship between BMI and mortality. Primary Funding Source: None.

Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing

Background: Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP). Objective: To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP. Design: Longitudinal, prospective cohort study. Setting: Online survey before and 6 months after results. Participants: DTC PGT consumers. Measurements: Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCP's understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses. Results: Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%). Limitation: Participants may not be representative of all DTC PGT consumers. Conclusion: A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve. Primary Funding Source: National Institutes of Health.

Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial: Annals of Internal Medicine: Vol 164, No 3

Background: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). Design: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917) Setting: 4 teaching hospitals. Participants: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. Intervention: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). Measurements: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. Results: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, −1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, −1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOE ε4 allele, distress was lower in the AD+CAD groups (difference, −4.8 [CI, −8.6 to −1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. Limitations: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. Conclusion: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. Primary Funding Source: National Human Genome Research Institute.

Antibody Response to a Fourth Messenger RNA COVID-19 Vaccine Dose in Kidney Transplant Recipients: A Case Series