Dynamic models augmented by hierarchical data: an application of estimating HIV epidemics at sub-national level.

Dynamic models have been successfully used in producing estimates of HIV epidemics at the national level due to their epidemiological nature and their ability to estimate prevalence, incidence, and mortality rates simultaneously. Recently, HIV interventions and policies have required more information at sub-national levels to support local planning, decision-making and resource allocation. Unfortunately, many areas lack sufficient data for deriving stable and reliable results, and this is a critical technical barrier to more stratified estimates. One solution is to borrow information from other areas within the same country. However, directly assuming hierarchical structures within the HIV dynamic models is complicated and computationally time-consuming. In this article, we propose a simple and innovative way to incorporate hierarchical information into the dynamical systems by using auxiliary data. The proposed method efficiently uses information from multiple areas within each country without increasing the computational burden. As a result, the new model improves predictive ability and uncertainty assessment.

Testing Mechanical Properties of Silicone Gel-Filled Breast Implants and Their Degradation.

Breast augmentation procedures using silicone implants have become increasingly popular over the past six decades. This article addresses the concerns of patients regarding implant strength by providing clinicians with valuable information in addition to video and pictorial evidence to share, fostering reassurance. The article focuses on the structural integrity and stability of breast implants, which play a critical role in their long-term performance and patient satisfaction. Specifically, it examines the industry standards outlined by the International Organization for Standardization (ISO), with a particular emphasis on ISO14607-2018, which encompasses a range of mechanical and physio-mechanical tests, including the assessment of silicone gel-fill firmness, evaluation of shell integrity, and examination of the impact of environmental conditions on implant performance. Breast implants are not static devices and are subject to aging and fatigue-based degradation. This emphasizes the need for ongoing monitoring and evaluation to ensure the long-term safety and satisfaction of patients. By providing a comprehensive examination of breast implant structure and industry standards, this article equips clinicians with the necessary knowledge to address patient concerns and foster confidence in the safety and longevity of breast augmentation procedures using silicone implants.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Assessing the Effectiveness of a Short Form Screening Tool (COPs) for Body Dysmorphic Disorder in Cosmetic Surgery Patients: A Study of Pre- and Post-Operative Outcomes.

Recent regulatory changes in Australian cosmetic surgery necessitate preoperative screening for body dysmorphic disorder (BDD). This study, which focuses on patient outcomes, evaluates the COPs tool's efficacy and examines its implications on patients undergoing cosmetic procedures. A total of 189 patients were included: 78 underwent Medicare-classified "cosmetic" surgeries, and 111 underwent "medically necessary" procedures. Patients completed the COPs assessment pre- and post-operatively, with a score >40 indicating BDD susceptibility. Results show no significant pre- to post-operative change in COPs scores across different surgical procedures (body, breast, facial, and mixed) in both "cosmetic" (p = 0.2-0.4) and "itemised" groups (p = 0.15-0.33). However, overall, there was a marked reduction in COPs scores post-operatively (p < 0.001), indicating improved self-perception. Specifically, 91% of patients initially BDD-prone showed scores < 40 post-operatively. Conversely, 3.8% of initially low-scoring patients developed BDD-prone scores post-operatively. Comparison between cosmetic and itemised groups revealed higher preoperative COPs scores in the itemised group (p = 0.006), though post-operative scores did not differ significantly (p = 0.33). Incidences of post-operative BDD-prone scores or scores < 40 did not differ between groups (p = 0.61). Complication rates and the need for revision surgery were similar between groups. These findings suggest two plausible interpretations: First, preoperative screening with the COPs tool may positively influence self-perception related to BDD among cosmetic surgery patients, potentially serving as a therapeutic adjunct for those at risk. Second, while screening tools are beneficial, they may have limitations in predicting post-operative outcomes related to BDD development. Further research should explore these dynamics to refine screening practices and optimise patient outcomes in cosmetic surgery contexts. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Formulation and acceptability of local nutrient-dense foods for young children: A formative study for the Child Health, Agriculture and Integrated Nutrition (CHAIN) Trial in rural Zimbabwe.

Stunting affects almost one-quarter of children globally, leading to reduced human capacity and increased long-term risk of chronic disease. Despite intensive infant and young child feeding (IYCF) interventions, many children do not meet their requirements for essential nutrients. This study aimed to assess the feasibility of implementing an IYCF intervention utilizing nutrient-dense powders from egg, biofortified sugar beans and Moringa oleifera leaf in rural Zimbabwe. A mixed-methods formative study was conducted comprising the following: (i) a recipe formulation trial, (ii) trials of improved practices to assess acceptability of the intervention, and (iii) a participatory message formulation process to develop counselling modules for the IYCF-plus intervention. Twenty-seven mother-baby pairs were recruited between November 2019 and April 2020. Key domains affecting IYCF practices that emerged were time, emotional and physical space, cultural and religious beliefs, indigenous knowledge systems and gender dynamics. Household observations and sensory evaluation indicated high acceptability of the new ingredients. Recipe formulation and participatory message formulation by participants instilled community ownership and served to demystify existing misconceptions about the new food products. Families noted the potential for intervention sustainability because the foods could be grown locally. Supplementing complementary foods with nutrient-dense local food ingredients as powders has the potential to sustainably address nutrient-gaps in the diets of young children living in rural lower- and middle-income countries. Comprehensive IYCF counselling utilizing a gender-lens approach, family support and indigenous knowledge systems or resources are key elements to support positive behaviour change in complementary feeding interventions.

The Effect of Drains and Compressive Garments Versus Progressive Tensioning Sutures on Seroma Formation in Abdominoplasty.

Seroma is a common problem following abdominoplasty surgery. Both compressive garments with drains and progressive tension sutures have their advocates to minimise seroma formation. This is a retrospective study in which patients underwent an identical surgical procedure, except for use of drains and garments in comparison to progressive tension sutures between 2005 and 2020. Two hundred thirty-two patients were included in the study 61 in the drains and garment group (DG group), and 171 with progressive tension sutures (PTS group) alone. There was a lower incidence of seroma formation in the PTS group (X2 (1, N = 232) = 6.35, P = .012). The weight of tissue excised in the PTS group was greater than the DG group (P < .001). There was there a significantly higher tissue excision weights for patients who developed a seroma, compared with those who did not (P=.02). Patients, who developed a seroma in the PTS group, had significantly greater excision weights than the DG group. Liposuction did not change the incidence of seroma in each group (X2 (4, N = 232) = 6.701, P = .08 n/s). This study demonstrates the effectiveness of progressive tension sutures in reducing the incidence of seroma formation following abdominoplasty, particularly when large excision weights are involved. The addition of small volume liposuction distant to the abdominal flap does not increase the incidence of seroma formation.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Biomechanical Principles of Breast Implants and Current State of Research in Soft Tissue Engineering for Cosmetic Breast Augmentation.

Currently there are limited implant-based options for cosmetic breast augmentation, and problems associated with those have been increasingly appreciated, most commonly capsular contracture, which occurs due to a chronic foreign body reaction against non-degradable implant materials such as silicone and polyurethane leading to scar tissue formation, pain, and deformity. The underlying biomechanical concepts with implants create a reciprocal stress-strain relationship with local tissue, whilst acting as a deforming force. This means that with time, as the implant continues to have an effect on surrounding tissue the implant and host's biomechanical properties diverge, making malposition, asymmetry, and other complications more likely. Research directed towards development of alternative therapies based on tissue engineering and regenerative medicine seeks to optimize new tissue formation through modulation of tissue progenitors and facilitating tissue regeneration. Scaffolds can guide the process of new tissue formation by providing both an implant surface and a three-dimensional space that promotes the development of a microenvironment that guides attachment, migration, proliferation, and differentiation of connective tissue progenitors. Important to scaffold design are the architecture, surface chemistry, mechanical properties, and biomaterial used. Scaffolds provide a void in which vascularization, new tissue formation, and remodelling can sequentially occur. They provide a conduit for delivery of the different cell types required for tissue regeneration into a graft site, facilitating their retention and distribution. Whilst recent research from a small number of groups is promising, there are still ongoing challenges to achieving clinical translation. This article summarizes the biomechanical principles of breast implants, how these impact outcomes, and progress in scaffold-guided tissue engineering approaches to cosmetic breast augmentation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030.

BACKGROUND: UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets. METHODS AND FINDINGS: We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections. CONCLUSIONS: The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.

Long-term laryngotracheal complications following cardiac surgery.

BACKGROUND AND AIM OF THE STUDY: Long-term laryngotracheal complications have not been described in adult patients undergoing cardiac surgery. The purpose of this study was to determine the incidence of and risk factors for laryngotracheal complications following cardiac surgery. METHODS: A retrospective chart review of patients at high risk for laryngotracheal complications following cardiac surgery between 2006 and 2016 was performed. High-risk patients were reviewed to determine the presence of laryngotracheal complications including laryngotracheal stenosis, keyhole deformity, or vocal cord immobility. Logistic regression was used to identify predictors of long-term laryngotracheal complications. RESULTS: Of 11,417 patients who underwent cardiac surgery, 1099 were identified as at high risk. Of these, 24 (2.2%) developed laryngotracheal complications following their surgery and intensive care unit (ICU) stay. Laryngotracheal stenosis and keyhole deformity were present in 13 (1.2%) and 6 (0.5%) patients, respectively. Logistic regression demonstrated older age (age ≥ 70 odds ratio [OR] 0.31, 95% confidence interval [CI] 0.12-0.83) was protective, while readmission to ICU for ventilation (OR 3.11, 95% CI 1.17-8.25) and receiving a tracheostomy (OR 7.83, 95% CI 2.22-27.6) were associated with laryngotracheal complications. CONCLUSIONS: The incidence of long-term laryngotracheal complications following cardiac surgery was 2.2%. Readmission to ICU for ventilation and having a tracheostomy performed were associated with laryngotracheal complications.

Plane Change Vs Capsulotomy: A Comparison of Treatments for Capsular Contraction in Breast Augmentation Using the Subfascial Plane.

BACKGROUND: The management of capsular contraction following breast augmentation has numerous, often conflicting potential treatment protocols, each designed to reduce the incidence of further recurrence. The use of the subfascial plane has not been investigated as an alternative to other treatment options. OBJECTIVES: To examine the outcomes from patients presenting with recurrent capsular contraction after being treated for the first capsule by placement of an implant into the subfascial (SF) plane. METHODS: Retrospective analysis of 111 case notes of patients who presented with capsular contraction. 65 had undergone SF augmentation, 17 submuscular (SM) and 29 subglandular (SG) placement of implant at the primary procedure. At a secondary procedure, those with SF implants underwent open capsulotomy and those with SM and SG implants underwent a change in plane to SF. RESULTS: There is a significant difference in the proportion of patients that developed a capsule following the second surgery between the groups that had undergone capsulotomy (SF = 16.9%) or plane change (SM = 47% and SG = 37.9%, X2 (2,111) = 8.6, P = 0.02). When recurrence at the same site was examined, there was also a significant difference between the groups (X2 (2111) = 10.7, P < 0.01). A ruptured implant significantly increased the incidence of further capsular contraction when in the SG plane (X2 (2,29) = 12.1, P < 0.01). CONCLUSIONS: In the absence of implant rupture, changing the plane of an implant to a SF position at revision surgery does not reduce the incidence of subsequent capsular contracture compared with open capsulotomy. Open capsulotomy is a reasonable choice following recurrence of capsular contraction following initial SF placement. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Renal failure parathyroidectomy - Is pre-operative imaging worthwhile?

BACKGROUND: Tertiary hyperparathyroidism is a significant issue in renal failure patients and some require surgery to control their serum calcium. A number of imaging techniques are used to localise the position of the parathyroid glands prior to surgery. Currently, a combination of ultrasound and isotope preoperative localisation imaging is accepted as useful in parathyroid surgery for primary disease. However, the use of pre-operative imaging in parathyroid surgery in renal failure patients is uncertain. The role of pre-operative imaging of the parathyroid glands in patients with renal failure hyperparathyroidism was assessed with imaging outcomes compared to operative and pathological findings in two cohorts of patients undergoing parathyroid surgery - primary and tertiary. METHODS: All data were collected prospectively over a 10-year period (2003-2013) from the practice of a single surgeon. Patients were grouped into either primary hyperparathyroidism (49 patients) or tertiary hyperparathyroidism (41 patients). The majority, 63 of 90 (70%) patients, underwent both ultrasound (US) and isotope (MIBI) pre-operative imaging. Pre-operative imaging was correlated with operative and pathological findings. FINDINGS: Comparison of the results of the two groups using ordinal regression analysis confirmed these imaging techniques are significantly more accurate in primary than tertiary parathyroid surgery (p = 0.022). CONCLUSIONS: While accepted practice of pre-operative combined USS and MIBI imaging is essential in unilateral imaged-focused neck exploration for primary disease, these imaging techniques have a more limited use pre-operatively in renal failure parathyroidectomy.

Decision Tree Pattern Recognition Model for Radio Frequency Interference Suppression in NQR Experiments.

Radio frequency interference places a major limitation on the in-situ use of unshielded nuclear quadrupole or nuclear magnetic resonance methods in industrial environments for quality control and assurance applications. In this work, we take the detection of contraband in an airport security-type application that is subject to burst mode radio frequency interference as a test case. We show that a machine learning decision tree model is ideally suited to the automated identification of interference bursts, and can be used in support of automated interference suppression algorithms. The usefulness of the data processed additionally by the new algorithm compared to traditional processing is shown in a receiver operating characteristic (ROC) analysis of a validation trial designed to mimic a security contraband detection application. The results show a highly significant increase in the area under the ROC curve from 0.580 to 0.906 for the proper identification of recovered data distorted by interfering bursts.

A Different Perspective on Breast Implant Surface Texturization and Anaplastic Large Cell Lymphoma (ALCL).

Anaplastic large cell lymphoma (ALCL) is a rare form of lymphoma involving cells of the immune system. It is currently gaining interest because of an association between the development of ALCL and an increased risk in women who have had breast implant surgery. Although not confirmed, many theories exist as to the etiology of this association in women, and there is growing concern that ALCL is more prevalent in women with textured breast implants. In particular, the risk of developing ALCL appears to be related to increasing implant texturization or "surface roughness." This paper examines the current manner of defining and characterizing breast implant surface texture and challenges the appropriateness of applying this technology and linking it to ALCL. It is not a comprehensive review of the etiology of capsular contracture and ALCL, but it proposes an alternative perspective on surface texture measurements from that currently employed and its role in researching the etiology of ALCL. The authors hope that their article will provoke thought and reflection when considering the issues currently being highlighted with regard to texturing of breast implants.

Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern Ireland, 2000-2015.

Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000-2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa. Treatment outcomes were worse for patients with than without acquired resistance. Although acquired resistance is rare in the study area, certain patient groups are at higher risk. Identifying these patients and ensuring that adequate resources are available for treatment may prevent acquisition of resistance, thereby limiting transmission of drug-resistant strains of mycobacteria.

The use of whole-genome sequencing in cluster investigation of a multidrug-resistant tuberculosis outbreak.

We used whole-genome sequencing (WGS) to delineate transmission networks and investigate the benefits of WGS during cluster investigation.We included clustered cases of multidrug-resistant (MDR) tuberculosis (TB)/extensively drug-resistant (XDR) TB linked by mycobacterial interspersed repetitive unit variable tandem repeat (MIRU-VNTR) strain typing or epidemiological information in the national cluster B1006, notified between 2007 and 2013 in the UK. We excluded from further investigation cases whose isolates differed by greater than 12 single nucleotide polymorphisms (SNPs). Data relating to patients' social networks were collected.27 cases were investigated and 22 had WGS, eight of which (36%) were excluded as their isolates differed by more than 12 SNPs to other cases. 18 cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in seven out of 18 cases (39%) in the transmission network following WGS and epidemiological investigation.This investigation of a drug-resistant TB cluster illustrates the opportunities and limitations of WGS in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However, not every cluster will be solvable, regardless of the quality of genomic data.

Variation in Leaf Respiration Rates at Night Correlates with Carbohydrate and Amino Acid Supply.

Plant respiration can theoretically be fueled by and dependent upon an array of central metabolism components; however, which ones are responsible for the quantitative variation found in respiratory rates is unknown. Here, large-scale screens revealed 2-fold variation in nighttime leaf respiration rate (RN) among mature leaves from an Arabidopsis (Arabidopsis thaliana) natural accession collection grown under common favorable conditions. RN variation was mostly maintained in the absence of genetic variation, which emphasized the low heritability of RN and its plasticity toward relatively small environmental differences within the sampling regime. To pursue metabolic explanations for leaf RN variation, parallel metabolite level profiling and assays of total protein and starch were performed. Within an accession, RN correlated strongly with stored carbon substrates, including starch and dicarboxylic acids, as well as sucrose, major amino acids, shikimate, and salicylic acid. Among different accessions, metabolite-RN correlations were maintained with protein, sucrose, and major amino acids but not stored carbon substrates. A complementary screen of the effect of exogenous metabolites and effectors on leaf RN revealed that (1) RN is stimulated by the uncoupler FCCP and high levels of substrates, demonstrating that both adenylate turnover and substrate supply can limit leaf RN, and (2) inorganic nitrogen did not stimulate RN, consistent with limited nighttime nitrogen assimilation. Simultaneous measurements of RN and protein synthesis revealed that these processes were largely uncorrelated in mature leaves. These results indicate that differences in preceding daytime metabolic activities are the major source of variation in mature leaf RN under favorable controlled conditions.

Efficacy of a Clinic-Based Safer Sex Program for Human Immunodeficiency Virus-Uninfected and Human Immunodeficiency Virus-Infected Young Black Men Who Have Sex With Men: A Randomized Controlled Trial.

OBJECTIVE: To test the efficacy of a single-session, clinic-based intervention designed to promote condom use among young black men who have sex with men (YBMSM). METHODS: Six hundred YBMSM were enrolled in a randomized controlled trial, using a 12-month observation period. An intent-to-treat analysis was performed, with multiple imputation for missing data. RESULTS: Compared with the reference group, human immunodeficiency virus (HIV)-infected men in the intervention group had 64% greater odds of reporting consistent condom use for anal receptive sex over 12 months (estimated odds ratio, 1.64; 95% confidence interval, 1.23-2.17, P = 0.001). Also, compared with the reference group, HIV-uninfected men in the intervention group had more than twice the odds of reporting consistent condom use for anal receptive sex over 12 months (estimated odds ratio, 2.14; 95% confidence interval, 1.74-2.63, P < 0.001). Significant intervention effects relative to incident sexually transmitted diseases were not observed. CONCLUSIONS: A single-session, clinic-based, intervention may help protect HIV-uninfected YBMSM against HIV acquisition and HIV-infected YBMSM from transmitting the virus to insertive partners.

Keeping Disability in Mind: A Case Study in Implantable Brain-Computer Interface Research.

Brain-Computer Interface (BCI) research is an interdisciplinary area of study within Neural Engineering. Recent interest in end-user perspectives has led to an intersection with user-centered design (UCD). The goal of user-centered design is to reduce the translational gap between researchers and potential end users. However, while qualitative studies have been conducted with end users of BCI technology, little is known about individual BCI researchers' experience with and attitudes towards UCD. Given the scientific, financial, and ethical imperatives of UCD, we sought to gain a better understanding of practical and principled considerations for researchers who engage with end users. We conducted a qualitative interview case study with neural engineering researchers at a center dedicated to the creation of BCIs. Our analysis generated five themes common across interviews. The thematic analysis shows that participants identify multiple beneficiaries of their work, including other researchers, clinicians working with devices, device end users, and families and caregivers of device users. Participants value experience with device end users, and personal experience is the most meaningful type of interaction. They welcome (or even encourage) end-user input, but are skeptical of limited focus groups and case studies. They also recognize a tension between creating sophisticated devices and developing technology that will meet user needs. Finally, interviewees espouse functional, assistive goals for their technology, but describe uncertainty in what degree of function is "good enough" for individual end users. Based on these results, we offer preliminary recommendations for conducting future UCD studies in BCI and neural engineering.

Insidious Risk of Severe Mycobacterium chimaera Infection in Cardiac Surgery Patients.

BACKGROUND: An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. METHODS: Parallel investigations were pursued: (1) identification of cardiopulmonary bypass-associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. RESULTS: Eighteen probable cases of cardiopulmonary bypass-associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81-87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. CONCLUSIONS: We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.