An evaluation of physical and augmented patient-specific intracranial aneurysm simulators on microsurgical clipping performance and skills: a randomized controlled study.

OBJECTIVE: In the era of flow diversion, there is an increasing demand to train neurosurgeons outside the operating room in safely performing clipping of unruptured intracranial aneurysms. This study introduces a clip training simulation platform for residents and aspiring cerebrovascular neurosurgeons, with the aim to visualize peri-aneurysm anatomy and train virtual clipping applications on the matching physical aneurysm cases. METHODS: Novel, cost-efficient techniques allow the fabrication of realistic aneurysm phantom models and the additional integration of holographic augmented reality (AR) simulations. Specialists preselected suitable and unsuitable clips for each of the 5 patient-specific models, which were then used in a standardized protocol involving 9 resident participants. Participants underwent four sessions of clip applications on the models, receiving no interim training (control), a video review session (video), or a video review session and holographic clip simulation training (video + AR) between sessions 2 and 3. The study evaluated objective microsurgical skills, which included clip selection, number of clip applications, active simulation time, wrist tremor analysis during simulations, and occlusion efficacy. Aneurysm occlusions of the reference sessions were assessed by indocyanine green videoangiography, as well as conventional and photon-counting CT scans. RESULTS: A total of 180 clipping procedures were performed without technical complications. The measurements of the active simulation times showed a 39% improvement for all participants. A median of 2 clip application attempts per case was required during the final session, with significant improvement observed in experienced residents (postgraduate year 5 or 6). Wrist tremor improved by 29% overall. The objectively assessed aneurysm occlusion rate (Raymond-Roy class 1) improved from 76% to 80% overall, even reaching 93% in the extensively trained cohort (video + AR) (p = 0.046). CONCLUSIONS: The authors introduce a newly developed simulator training platform combining physical and holographic aneurysm clipping simulators. The development of exchangeable, aneurysm-comprising housings allows objective radio-anatomical evaluation through conventional and photon-counting CT scans. Measurable performance metrics serve to objectively document improvements in microsurgical skills and surgical confidence. Moreover, the different training levels enable a training program tailored to the cerebrovascular trainees' levels of experience and needs.

A conforming auxiliary space preconditioner for the mass conserving stress-yielding method.

We are studying the efficient solution of the system of linear equations stemming from the mass conserving stress-yielding (MCS) discretization of the Stokes equations. We perform static condensation to arrive at a system for the pressure and velocity unknowns. An auxiliary space preconditioner for the positive definite velocity block makes use of efficient and scalable solvers for conforming Finite Element spaces of low order and is analyzed with emphasis placed on robustness in the polynomial degree of the discretization. Numerical experiments demonstrate the potential of this approach and the efficiency of the implementation.

Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers.

BACKGROUND: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs). METHODS: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring. RESULTS: Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response. CONCLUSIONS: HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Impact of diagnostic strategies for tuberculosis using lateral flow urine lipoarabinomannan assay in people living with HIV.

BACKGROUND: Tuberculosis is the primary cause of hospital admission in people living with HIV, and the likelihood of death in the hospital is unacceptably high. The Alere Determine TB LAM Ag test (AlereLAM) is a point-of-care test and the only lateral flow lipoarabinomannan assay (LF-LAM) assay currently commercially available and recommended by the World Health Organization (WHO). A 2019 Cochrane Review summarised the diagnostic accuracy of LF-LAM for tuberculosis in people living with HIV. This systematic review assesses the impact of the use of LF-LAM (AlereLAM) on mortality and other patient-important outcomes. OBJECTIVES: To assess the impact of the use of LF-LAM (AlereLAM) on mortality in adults living with HIV in inpatient and outpatient settings. To assess the impact of the use of LF-LAM (AlereLAM) on other patient-important outcomes in adults living with HIV, including time to diagnosis of tuberculosis, and time to initiation of tuberculosis treatment. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded (Web of Science), BIOSIS Previews, Scopus, LILACS; ProQuest Dissertations and Theses; ClinicalTrials.gov; and the WHO ICTRP up to 12 March 2021. SELECTION CRITERIA: Randomized controlled trials that compared a diagnostic intervention including LF-LAM with diagnostic strategies that used smear microscopy, mycobacterial culture, a nucleic acid amplification test such as Xpert MTB/RIF, or a combination of these tests. We included adults (≥ 15 years) living with HIV. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, and analysed risk of bias using the Cochrane tool for assessing risk of bias in randomized studies. We contacted study authors for clarification as needed. We used risk ratio (RR) with 95% confidence intervals (CI). We used a fixed-effect model except in the presence of clinical or statistical heterogeneity, in which case we used a random-effects model. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included three trials, two in inpatient settings and one in outpatient settings. All trials were conducted in sub-Saharan Africa and assessed the impact of diagnostic strategies that included LF-LAM on mortality when the test was used in conjunction with other tuberculosis diagnostic tests or clinical assessment for clinical decision-making in adults living with HIV. Inpatient settings  In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy likely reduces mortality in people living with HIV at eight weeks compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 0.85, 95% CI 0.76 to 0.94; 5102 participants, 2 trials; moderate-certainty evidence). That is, people living with HIV who received LF-LAM had 15% lower risk of mortality. The absolute effect was 34 fewer deaths per 1000 (from 14 fewer to 55 fewer). In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy probably results in a slight increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 1.26, 95% CI 0.94 to 1.69; 5102 participants, 2 trials; moderate-certainty evidence).  Outpatient settings In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality in people living with HIV at six months compared to routine tuberculosis diagnostic testing without LF-LAM (RR 0.89, 95% CI 0.71 to 1.11; 2972 participants, 1 trial; low-certainty evidence). Although this trial did not detect a difference in mortality, the direction of effect was towards a mortality reduction, and the effect size was similar to that in inpatient settings.  In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may result in a large increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (RR 5.44, 95% CI 4.70 to 6.29, 3022 participants, 1 trial; low-certainty evidence). Other patient-important outcomes Assessment of other patient-important and implementation outcomes in the trials varied. The included trials demonstrated that a higher proportion of people living with HIV were able to produce urine compared to sputum for tuberculosis diagnostic testing; a higher proportion of people living with HIV were diagnosed with tuberculosis in the group that received LF-LAM; and the incremental diagnostic yield was higher for LF-LAM than for urine or sputum Xpert MTB/RIF. AUTHORS' CONCLUSIONS: In inpatient settings, the use of LF-LAM as part of a tuberculosis diagnostic testing strategy likely reduces mortality and probably results in a slight increase in tuberculosis treatment initiation in people living with HIV. The reduction in mortality may be due to earlier diagnosis, which facilitates prompt treatment initiation. In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality and may result in a large increase in tuberculosis treatment initiation in people living with HIV. Our results support the implementation of LF-LAM to be used in conjunction with other WHO-recommended tuberculosis diagnostic tests to assist in the rapid diagnosis of tuberculosis in people living with HIV.

One Health Education for Future Physicians: A Case Report of Cat-Transmitted Sporotrichosis.

A healthy 35-year-old Brazilian woman presented with persistent redness, swelling, and multiple wounds on the hand 2 weeks after a cat bite in her home country. She was treated twice with amoxicillin-clavulanate but failed to demonstrate improvement. She then presented to our institution with a newly developed abscess on the right hand. Incision and drainage were performed and she was admitted to the hospital. She was subsequently treated with broad-spectrum antibiotics. Her symptoms improved but did not resolve. Four days after hospital discharge, a wound culture resulted as positive for Sporothrix schenchii. The patient was treated with itraconazole. Sporotrichosis is endemic in many countries including Brazil and is known to be transmitted by cat bites. Sporotrichosis should be considered in the differential diagnosis for patients who have symptoms of cellulitis after cat bites in an endemic area.

Divergence-free tangential finite element methods for incompressible flows on surfaces.

In this work we consider the numerical solution of incompressible flows on two-dimensional manifolds. Whereas the compatibility demands of the velocity and the pressure spaces are known from the flat case one further has to deal with the approximation of a velocity field that lies only in the tangential space of the given geometry. Abandoning H 1-conformity allows us to construct finite elements which are-due to an application of the Piola transformation-exactly tangential. To reintroduce continuity (in a weak sense) we make use of (hybrid) discontinuous Galerkin techniques. To further improve this approach, H ( div Γ ) -conforming finite elements can be used to obtain exactly divergence-free velocity solutions. We present several new finite element discretizations. On a number of numerical examples we examine and compare their qualitative properties and accuracy.

Top Questions in the Diagnosis and Treatment of Pulmonary M. abscessus Disease.

Mycobacterium abscessus disease is particularly challenging to treat, given the intrinsic drug resistance of this species and the limited data on which recommendations are based, resulting in a greater reliance on expert opinion. We address several commonly encountered questions and management considerations regarding pulmonary Mycobacterium abscessus disease, including the role of subspecies identification, diagnostic criteria for determining disease, interpretation of drug susceptibility test results, approach to therapy including the need for parenteral antibiotics and the role for new and repurposed drugs, and the use of adjunctive strategies such as airway clearance and surgical resection.

Diagnostic Delays and Treatment Implications for Patients with Isoniazid-Resistant Tuberculosis: A Case Report and Review of the Literature.

Drug-resistant tuberculosis (DR-TB) remains a major public health threat. A 23-year-old man presented with fever, dyspnea, and a pleural effusion. After a delay, he was diagnosed with isoniazid (INH)-resistant TB. We review the literature describing the epidemiological and clinical significance of INH-resistant TB and its relevance for low-incidence countries, such as the United States.

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital.

BACKGROUND: Mozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established. METHODS: This study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated. RESULTS: Of 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%. CONCLUSIONS: There is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Knowledge of Human Immunodeficiency Virus Status and Seropositivity After a Recently Negative Test in Malawi.

BACKGROUND: Awareness of human immunodeficiency virus (HIV) status among all people with HIV is critical for epidemic control. We aimed to assess accurate knowledge of HIV status, defined as concordance with serosurvey test results from the 2010 Malawi Demographic Health Survey (MDHS), and to identify risk factors for seropositivity among adults (aged 15-49) reporting a most recently negative test within 12 months. METHODS: Data were analyzed from the 2010 MDHS. A logistic regression model was constructed to determine factors independently associated with HIV seropositivity after a recently negative test. All analyses controlled for the survey's complex design. RESULTS: A total of 11 649 adults tested for HIV during this MDHS reported ever being sexually active. Among these, HIV seroprevalence was 12.0%, but only 61.7% had accurate knowledge of their status. Forty percent (40.3%; 95% confidence interval [CI], 36.8-43.8) of seropositive respondents reported a most recently negative test. Of those reporting that this negative test was within 12 months (n = 3630), seroprevalence was 7.2% for women (95% CI, 5.7-9.2), 5.2% for men (95% CI, 3.9-6.9), higher in the South, and higher in rural areas for men. Women with higher education and men in the richest quintile were at higher risk. More than 1 lifetime union was significantly associated with recent HIV infection, whereas never being married was significantly protective. CONCLUSIONS: Self-reported HIV status based on prior test results can underestimate seroprevalence. These results highlight the need for posttest risk assessment and support for people who test negative for HIV and repeat testing in people at high risk for HIV infection.

Agents of change: The role of healthcare workers in the prevention of nosocomial and occupational tuberculosis.

Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired well-being in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection (LTBI) can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission.

The role of the law in reducing tuberculosis transmission in Botswana, South Africa and Zambia.

OBJECTIVE: To determine whether laws and regulations in Botswana, South Africa and Zambia - three countries with a high tuberculosis and HIV infection burden - address elements of the World Health Organization (WHO) policy on tuberculosis infection control. METHODS: An online desk review of laws and regulations that address six selected elements of the WHO policy on tuberculosis infection control in the three countries was conducted in November 2015 using publicly available domestic legal databases. The six elements covered: (i) national policy and legal framework; (ii) health facility design, construction and use; (iii) tuberculosis disease surveillance among health workers; (iv) patients' and health workers' rights; (v) monitoring of infection control measures; and (vi) relevant research. FINDINGS: The six elements were found to be adequately addressed in the three countries' laws and regulations. In all three, tuberculosis case-reporting is required, as is tuberculosis surveillance among health workers. Each country's legal and regulatory framework also addresses the need to respect individuals' rights and privacy while safeguarding public health. These laws and regulations create a strong foundation for tuberculosis infection control. Although the legal and regulatory frameworks thoroughly address tuberculosis infection control, their dissemination, implementation and enforcement were not assessed, nor was their impact on public health. CONCLUSION: Laws and regulations in Botswana, South Africa and Zambia address all six selected elements of the WHO policy on tuberculosis infection control. However, the lack of data on their implementation is a limitation. Future research should assess the implementation and public health impact of laws and regulations.

Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature.

BACKGROUND: Powassan virus (POWV) is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits Lyme disease. The prevalence of POWV among animal hosts and vectors has been increasing. We present 8 cases of POWV encephalitis from Massachusetts and New Hampshire in 2013-2015. METHODS: We abstracted clinical and epidemiological information for patients with POWV encephalitis diagnosed at 2 hospitals in Massachusetts from 2013 to 2015. We compared their brain imaging with those in published findings from Powassan and other viral encephalitides. RESULTS: The patients ranged in age from 21 to 82 years, were, for the most part, previously healthy, and presented with syndromes of fever, headache, and altered consciousness. Infections occurred from May to September and were often associated with known tick exposures. In all patients, cerebrospinal fluid analyses showed pleocytosis with elevated protein. In 7 of 8 patients, brain magnetic resonance imaging demonstrated deep foci of increased T2/fluid-attenuation inversion recovery signal intensity. CONCLUSIONS: We describe 8 cases of POWV encephalitis in Massachusetts and New Hampshire in 2013-2015. Prior to this, there had been only 2 cases of POWV encephalitis identified in Massachusetts. These cases may represent emergence of this virus in a region where its vector, I. scapularis, is known to be prevalent or may represent the emerging diagnosis of an underappreciated pathogen. We recommend testing for POWV in patients who present with encephalitis in the spring to fall in New England.