Effects of Workplace Violence on Emotional Distress.

The current study assessed the effects of workplace violence (WPV) and fear related to WPV on community mental health (CMH) workers' emotional distress. This cross-sectional study used structural equation modeling (SEM) and comprised participants who were CMH workers in Korea. We used WPV questionnaires and the Korean version of the Patient-Reported Outcomes Measurement Information System® item bank to evaluate emotional distress. SEM data from 763 workers revealed significant positive effects of WPV on anxiety (ß = 0.23, p = 0.009) and anger (ß = 0.26, p = 0.007), and significant positive effects of fear related to WPV on anxiety (ß = 0.21, p = 0.004) and anger (ß = 0.19, p = 0.002). Preventive measures significantly mediated the relationship between WPV and emotional distress and between fear related to WPV and emotional distress. Findings verified the relationship between WPV and workers' emotional distress and the mediating role of preventive measures. [Journal of Psychosocial Nursing and Mental Health Services, 62(4), 24-32.].

Characteristics of the Mycoplasma pneumoniae Epidemic from 2019 to 2020 in Korea: Macrolide Resistance and Co-Infection Trends.

Mycoplasma pneumoniae, a major etiological agent of community-acquired pneumonia, exhibits distinct cyclic epidemic patterns recurring every three to five years. Several cases of co-infection with severe acute respiratory syndrome coronavirus 2 have been reported globally, resulting in unfavorable clinical manifestations. This study investigated the epidemiological features of the recent M. pneumoniae outbreak (May 2019-April 2020) using retrospective data from the last five years. Molecular test data for macrolide resistance and co-infection were obtained from the Seegene Medical Foundation. National medical expenditure and hospitalization rates were analyzed using data from The Health Insurance Review and Assessment Service of Korea. The macrolide resistance rate was 69.67%, peaking at 71.30% during the epidemic period, which was considerably higher than the 60.89% rate during non-epidemic periods. The co-infection rate with other respiratory pathogens was 88.49%; macrolide-resistant M. pneumoniae strains showed a 2.33% higher co-infection rate than the susceptible strains. The epidemic period had 15.43% higher hospitalization and 78.27% higher medical budget expenditure per patient than non-epidemic periods. The increased rates of macrolide resistance and co-infection observed in macrolide-resistant M. pneumoniae during the epidemic period highlight the importance of monitoring future outbreaks, especially considering macrolide resistance and the risk of co-infection with other pathogens.

Workplace Violence Experienced by Community Mental Health Workers.

A cross-sectional online survey was conducted to 1) investigate the prevalence of workplace violence and workers' emotional distress, 2) explore factors associated with workplace violence, and 3) assess workers' needs for preventive measures. A total of 763 community mental health workers participated in Korea. Among them, 85.85% of workers experienced workplace violence, including verbal (74.31%), emotional (66.45%), infectious (47.44%), informational (42.60%), sexual (32.50%), and physical (23.72%) abuse. Binary logistic regression analysis indicated that sex, occupation, certification, and working institution were significantly associated with workplace violence. Workplace violence affects workers' depression, anger, and anxiety negatively. The most-needed preventive measure is a two-person home visit.

Effects of Positive Psychotherapy for People with Psychosis: A Systematic Review and Meta-Analysis.

This study evaluates positive psychotherapy's effects on the well-being and psychiatric symptoms of people with psychosis. A systematic search was conducted using 10 electronic databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was performed using the R 4.2.0 program to estimate the effect size. Seventeen studies were included in the systematic review and 14 in meta-analysis. Positive psychotherapy for people with psychosis had significant effects on subjective and psychological well-being and psychiatric symptoms. Further, country, age, and session were significant moderators. Thus, positive psychotherapy improves the well-being and psychiatric symptoms of people with psychosis.

Human Rights of Persons With Mental Illness After the Korean Mental Health Act Revision: A Qualitative Study.

After the Constitutional Court of Korea ruled that the provision of involuntary admissions was unconstitutional, as it violates personal freedom, the Mental Health and Welfare Act was amended in 2016. The current study explores involuntary admission and discharge experiences, after the law's revision, from a patient-centered perspective and suggests future directions to protect human rights. Data were collected from seven persons with mental illness and three family members through in-depth individual interviews and analyzed using thematic analysis. Persons with mental illness were still not guaranteed full autonomy and the right to receive proper treatment due to lack of mental health resources. The burden on family caregivers was amplified by stricter admission requirements. These results indicate the need for human rights-friendly emergency services, including peer crisis shelters and procedural assistance services. The government should develop community-based mental health services to ensure continuity of care without imposing public responsibility on family members. [Journal of Psychosocial Nursing and Mental Health Services, 60(8), 27-35.].

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Evaluation of Five User-Friendly Whole Genome Sequencing Software for Mycobacterium tuberculosis in Clinical Application.

BACKGROUND: Whole genome sequencing (WGS) is an increasingly useful tool for tuberculosis (TB) diagnosis and disease management. In this study, we evaluated the utility of user-friendly WGS tools in reporting resistance profiles and identifying lineages of clinical TB isolates from South Korea. METHODS: Forty clinical samples from TB patients showing discrepancies between their rapid molecular and conventional drug susceptibility tests were used in this study. Among these clinical isolates, 37 strains were successfully evaluated via WGS software, using the GenTB, TB Profiler, PhyResSE, CASTB, and Mykrobe. RESULTS: More accurate and faster susceptibility results could be obtained with isoniazid than with rifampin. Using the phenotypic test as the gold standard, the isoniazid concordance rate between phenotypic drug susceptibility test (DST) and WGS (GenTB: 45.9%, TB profiler: 40.5%, PhyResSE: 40.5%, CASTB: 48.6%, and Mykrobe: 43.2%) was much higher than between phenotypic DST and rapid molecular genotypic DST (18.9%) among the 37 strains. In contrast, the rifampin concordance rate between phenotypic DST and WGS and that between phenotypic DST and rapid molecular genotypic DST was similar (81.1-89.2%). We also found novel mutations associated with INH in katG and ahpC gene region, not covered by the line probe assay. In addition, lineage analysis identified 81.1% of these samples as L2 East Asian lineage strains, and 18.9% as L4 Euro-American lineage strains. CONCLUSION: WGS may play a pivotal role in TB diagnosis and the detection of drug resistance, genetic diversity, and transmission dynamics in the near future because of its accuracy, speed, and extensibility.

Effects of the Mental Health and Welfare Law revision on schizophrenia patients in Korea: an interrupted time series analysis.

BACKGROUND: High rates of involuntary hospitalization and long lengths of stay have been problematic in Korea. To address these problems, the Mental Health and Welfare Law was revised in 2016, mainly to protect patient rights by managing involuntary admissions. The aim of this study was to evaluate the impact of the revised Mental Health and Welfare Law on deinstitutionalization by using routinely collected data from hospital admissions and continuity of mental health service use after hospital discharge as proxy measures of deinstitutionalization. METHODS: We used monthly-aggregated claims-based data with a principal or secondary diagnosis of schizophrenia from 2012 to 2019, collected by the National Health Insurance Service. Outcome variables included rates of first admission; discharges; re-admissions within 7, 30, and 90 days; outpatient visits after discharge within 7 and 30 days; and continuity of visits, at least once a month for 6 months after discharge. Using interrupted time series analysis, we estimated the change in levels and trends of the rates after revision, controlling for baseline level and trend. RESULTS: There was no significant change in first admission and discharge rates after the revision. Immediately after the revision, however, the rates of re-admission within 7 and 30 days dropped significantly, by 2.24% and 1.99%, respectively. The slopes of the re-admission rate decreased significantly, by 0.10% and 0.14%, respectively. The slopes of the re-admission rate within 90 days decreased (0.001%). The rates of outpatient visits within 7 and 30 days increased by 1.98% and 2.72%, respectively. The rate of continuous care showed an immediate 4.0% increase. CONCLUSIONS: The revision had slight but significant effects on deinstitutionalization, especially decreasing short-term re-admission and increasing immediate outpatient service utilization.

Risk Scoring System of Mortality and Prediction Model of Hospital Stay for Critically Ill Patients Receiving Parenteral Nutrition.

Predicting the clinical progression of intensive care unit (ICU) patients is crucial for survival and prognosis. Therefore, this retrospective study aimed to develop the risk scoring system of mortality and the prediction model of ICU length of stay (LOS) among patients admitted to the ICU. Data from ICU patients aged at least 18 years who received parenteral nutrition support for ≥50% of the daily calorie requirement from February 2014 to January 2018 were collected. In-hospital mortality and log-transformed LOS were analyzed by logistic regression and linear regression, respectively. For calculating risk scores, each coefficient was obtained based on regression model. Of 445 patients, 97 patients died in the ICU; the observed mortality rate was 21.8%. Using logistic regression analysis, APACHE II score (15-29: 1 point, 30 or higher: 2 points), qSOFA score ≥ 2 (2 points), serum albumin level < 3.4 g/dL (1 point), and infectious or respiratory disease (1 point) were incorporated into risk scoring system for mortality; patients with 0, 1, 2-4, and 5-6 points had approximately 10%, 20%, 40%, and 65% risk of death. For LOS, linear regression analysis showed the following prediction equation: log(LOS) = 0.01 × (APACHE II) + 0.04 × (total bilirubin) - 0.09 × (admission diagnosis of gastrointestinal disease or injury, poisoning, or other external cause) + 0.970. Our study provides the mortality risk score and LOS prediction equation. It could help clinicians to identify those at risk and optimize ICU management.

Performance of QuantaMatrix Microfluidic Agarose Channel system integrated with mycobacteria growth indicator tube liquid culture.

The QuantaMatrix Microfluidic Agarose Channel (QMAC) system was used for rapid drug susceptibility testing (DST). Here, we performed DST using QMAC integrated with the mycobacteria growth indicator tube (MGIT) liquid culture employing a specially designed cross agarose channel for the tuberculosis chip. MGIT-, QMAC-, and Löwenstein-Jensen (LJ)-DSTs were performed using 13 drugs. The protocol for QMAC-DST was optimized using the inoculum obtained after the disaggregation of Mycobacterium tuberculosis clumps in MGIT culture. The completion times of QMAC-DST and MGIT-DST were analyzed, and the results of all three DSTs were compared. Discrepant results were analyzed using line probe assays and DNA sequencing. Nontuberculous mycobacteria were distinguished using the ρ-nitrobenzoic acid inhibition test. The overall agreement rate of QMAT-DST and LJ-DST was 97.0% and that of QMAT-DST and MGIT-DST was 86.3%. An average turnaround time for DST was 5.4 days, which was considerably less than the time required for MGIT-DST. The overall time required to obtain DST results using QMAC-DST integrated with MGIT culture was an average of 18.6 days: 13.2 days for culture and identification and 5.4 days for DST. Hence, QMAC-DST integrated with liquid culture can be used to perform DSTs with short turnaround times and effective detection. KEY POINTS: • QMAC system can simultaneously perform phenotypic DST with 13 anti-TB drugs and PNB. • An optimized DST protocol led to a marked decrease in clumping in MGIT culture. • QMAC system integrated with MGIT liquid culture system reduced the turnaround time.

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

Bayesian network analysis incorporating genetic anchors complements conventional Mendelian randomization approaches for exploratory analysis of causal relationships in complex data.

Mendelian randomization (MR) implemented through instrumental variables analysis is an increasingly popular causal inference tool used in genetic epidemiology. But it can have limitations for evaluating simultaneous causal relationships in complex data sets that include, for example, multiple genetic predictors and multiple potential risk factors associated with the same genetic variant. Here we use real and simulated data to investigate Bayesian network analysis (BN) with the incorporation of directed arcs, representing genetic anchors, as an alternative approach. A Bayesian network describes the conditional dependencies/independencies of variables using a graphical model (a directed acyclic graph) with an accompanying joint probability. In real data, we found BN could be used to infer simultaneous causal relationships that confirmed the individual causal relationships suggested by bi-directional MR, while allowing for the existence of potential horizontal pleiotropy (that would violate MR assumptions). In simulated data, BN with two directional anchors (mimicking genetic instruments) had greater power for a fixed type 1 error than bi-directional MR, while BN with a single directional anchor performed better than or as well as bi-directional MR. Both BN and MR could be adversely affected by violations of their underlying assumptions (such as genetic confounding due to unmeasured horizontal pleiotropy). BN with no directional anchor generated inference that was no better than by chance, emphasizing the importance of directional anchors in BN (as in MR). Under highly pleiotropic simulated scenarios, BN outperformed both MR (and its recent extensions) and two recently-proposed alternative approaches: a multi-SNP mediation intersection-union test (SMUT) and a latent causal variable (LCV) test. We conclude that BN incorporating genetic anchors is a useful complementary method to conventional MR for exploring causal relationships in complex data sets such as those generated from modern "omics" technologies.

Low prevalence of MDR-TB in Lao PDR: results from the first national anti-tuberculosis drug resistance survey.

OBJECTIVE: To present results of the first national anti-tuberculosis (TB) drug resistance survey conducted in Lao PDR between May 2016 and August 2017 to determine the prevalence of resistance to first-line anti-TB drugs among new and previously treated pulmonary TB cases in the country. METHODS: Patients with sputum smear-positive pulmonary TB were enrolled from 42 TB laboratories distributed in 40 clusters throughout the country. Survey sites were selected using probability-proportional-to-size sampling among all diagnostic centres in the country. In addition to smear microscopy, all patients underwent Xpert MTB/RIF testing and those found positive to Mycobacterium tuberculosis underwent sputum culture and drug susceptibility testing using the proportion method on solid Löwenstein-Jensen medium. RESULTS: Among 1006 eligible patients, 946 sputum smear-positive and Xpert MTB/RIF positive (Mycobacterium tuberculosis detected) patients were included in the survey, comprising 897 new and 49 previously treated TB cases. The prevalence of rifampicin-resistant TB was 1.2% (95% CI: 0.5-2.0%, n = 11/897) among new cases and 4.1% (95% CI: 0-9.6%, n = 2/49) among previously treated cases. Among the 946 TB cases confirmed by Xpert MTB/RIF, phenotypic drug sensitivity testing was available for 820 (776 new and 44 previously treated). The prevalence of multidrug-resistant TB (MDR-TB) was 0.5% (95% CI: 0-1.0%, n = 4/776) among new cases and 2.3% (95% CI: 0-6.7%, n = 1/44) among previously treated cases. No resistance to second-line injectable agents nor to fluoroquinolones was detected among MDR-TB patients. CONCLUSIONS: The first national anti-TB drug resistance survey in Lao PDR demonstrated an encouragingly low prevalence of MDR-TB. The results appear lower than previous WHO estimates, and in line with the routine surveillance based on Xpert MTB/RIF testing (conducted among 50% of presumptive TB patients in 2017). The country should continue to expand its Xpert MTB/RIF network and strive to achieve universal drug susceptibility testing.

OBJECTIF: Présenter les résultats de la première surveillance nationale de la résistance aux médicaments antituberculeux, menée en République Démocratique Populaire (RDP) Lao entre mai 2016 et août 2017 afin de déterminer la prévalence de la résistance aux médicaments antituberculeux de première intention chez les nouveaux cas et les cas déjà traités de tuberculose (TB) pulmonaire dans le pays. MÉTHODES: Les patients atteints de TB pulmonaire à frottis d'expectoration positif ont été recrutés dans 42 laboratoires TB répartis dans 40 groupes à travers tout le pays. Les sites de surveillance ont été sélectionnés sur la base d'un échantillon probabiliste proportionnel à la taille parmi tous les centres de diagnostic du pays. Outre l'examen microscopique des frottis, tous les patients ont subi un test Xpert MTB/RIF et ceux trouvés positifs pour Mycobacterium tuberculosis ont subi une culture d'expectorations et un test de sensibilité aux médicaments en utilisant la méthode des proportions sur un milieu solide de Löwenstein-Jensen. RÉSULTATS: Parmi les 1.006 patients éligibles, 946 patients à frottis positif et Xpert MTB/RIF positif (Mycobacterium tuberculosis détecté) ont été inclus dans la surveillance, comprenant 897 nouveaux cas et 49 cas de TB déjà traités. La prévalence de la TB résistante à la rifampicine était de 1,2% (IC95%: 0,5-2,0%, n = 11/897) chez les nouveaux cas et de 4,1% (IC95%: 0-9,6%, n = 2/49) chez les cas traités. Parmi les 946 cas de TB confirmés par Xpert MTB/RIF, des tests de sensibilité phénotypique aux médicaments étaient disponibles pour 820 (776 nouveaux cas et 44 cas traités antérieurement). La prévalence de la TB multirésistante (TB-MDR) était de 0,5% (IC95%: 0-1,0%, n = 4/776) chez les nouveaux cas et de 2,3% (IC95%: 0 à 6,7%, n = 1/44) parmi les cas précédemment traités. Aucune résistance aux agents injectables de deuxième intention ni aux fluoroquinolones n'a été détectée chez les patients atteints de TB-MDR. CONCLUSIONS: La première surveillance nationale de la résistance aux médicaments antituberculeux menée en RDP Lao a révélé une prévalence rassurante de la TB-MDR. Les résultats apparaissent inférieurs aux estimations précédentes de l'OMS et conformes à la surveillance de routine basée sur le test Xpert MTB/RIF (menée auprès de 50% des patients atteints de TB présumée en 2017). Le pays devrait continuer à élargir son réseau Xpert MTB/RIF et s'efforcer d'atteindre des tests universels de sensibilité aux médicaments.

Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial.

BACKGROUND: Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) remain unsatisfactory, and long-term use of second-line anti-TB drugs is accompanied by the frequent occurrence of adverse events, low treatment compliance, and high costs. The development of new efficient regimens with shorter treatment durations for MDR-TB will solve these issues and improve treatment outcomes. METHODS: This study is a phase II/III, multicenter, randomized, open-label clinical trial of non-inferiority design comparing a new regimen to the World Health Organization-endorsed conventional regimen for fluoroquinolone-sensitive MDR-TB. The control arm uses a conventional treatment regimen with second-line drugs including injectables for 20-24 months. The investigational arm uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence of adverse events grade 3 and above as evaluated by the Common Terminology Criteria for Adverse Events. Based on an α = 0.025 level of significance (one-sided test), a power of 80%, and a < 10% difference in treatment success rate between the control and investigational arms (80% vs. 70%) when the anticipated actual success rate in the treatment group is assumed to be 90%, the number of participants needed per arm to show non-inferiority of the investigational regimen was calculated as 48. Additionally, assuming the proportion of fluoroquinolone-susceptible MDR-TB among participants as 50%, and 5% loss to follow-up, the number of participants is calculated as N/( 0.50 × 0.95), resulting in 102 persons per group (204 in total). DISCUSSION: This trial will reveal the effectiveness and safety of a new shorter regimen comprising four oral drugs, including delamanid, linezolid, levofloxacin, and pyrazinamide, for the treatment of fluoroquinolone-sensitive MDR-TB. Results from this trial will provide evidence for adopting a shorter and more convenient treatment regimen for MDR-TB. TRIAL REGISTRATION: ClincalTrials.gov, NCT02619994 . Registered on 2 December 2015.

Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

A comparison of methods for inferring causal relationships between genotype and phenotype using additional biological measurements.

Genome wide association studies (GWAS) have been very successful over the last decade at identifying genetic variants associated with disease phenotypes. However, interpretation of the results obtained can be challenging. Incorporation of further relevant biological measurements (e.g. 'omics' data) measured in the same individuals for whom we have genotype and phenotype data may help us to learn more about the mechanism and pathways through which causal genetic variants affect disease. We review various methods for causal inference that can be used for assessing the relationships between genetic variables, other biological measures, and phenotypic outcome, and present a simulation study assessing the performance of the methods under different conditions. In general, the methods we considered did well at inferring the causal structure for data simulated under simple scenarios. However, the presence of an unknown and unmeasured common environmental effect could lead to spurious inferences, with the methods we considered displaying varying degrees of robustness to this confounder. The use of causal inference techniques to integrate omics and GWAS data has the potential to improve biological understanding of the pathways leading to disease. Our study demonstrates the suitability of various methods for performing causal inference under several biologically plausible scenarios.

Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease.

Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant Mycobacterium abscessus subsp. abscessus This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.

Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.