Improving Medication Management for Inpatients with a Secondary Diagnosis of Parkinson Disease.

ABSTRACT: Patients who have Parkinson disease require individualized medication regimens to optimize care. A review of the medication management of patients admitted to a tertiary care hospital with a secondary diagnosis of Parkinson disease found significant departures from the patients' home regimen. Medication regimens are often altered by health care teams unfamiliar with Parkinson disease-specific care in order to conform to standard hospital medication orders and administration times, potentially resulting in increased patient falls, delirium, and mortality.A nurse-led multidisciplinary team consisting of pharmacy, nursing, informatics, neurology, and quality personnel implemented a quality improvement (QI) project between July 2020 and July 2022 to identify patients with Parkinson disease, including those with a secondary diagnosis and those undergoing deep brain stimulation, and customize medication management in order to reduce length of stay, mortality, falls, falls with harm, and 30-day readmissions. The QI project team also evaluated patient satisfaction with medication management.Among patients with a secondary diagnosis of Parkinson disease, the proportion who had medication histories conducted by a pharmacy staff member increased from a baseline of 53% to more than 75% per month. For all patients with Parkinson disease, those whose medication history was taken by a pharmacy staff member had orders matching their home regimen 89% of the time, whereas those who did not had orders matching the home regimen only 40% of the time. Among patients with a secondary diagnosis of Parkinson disease, the length-of-stay index decreased from a baseline of 1 to 0.94 and observed-to-expected mortality decreased from 1.03 to 0.78. The proportion of patients experiencing a fall decreased from an average of 5% to 4.08% per quarter, while the proportion of patients experiencing a fall with harm decreased from an average of 1% to 0.75% per quarter. The rate of 30-day readmissions decreased from 10.81% to 4.53% per quarter. Patient satisfaction scores were 1.95 points higher for patients who had medication histories taken by pharmacy than for those who did not (5 versus 3.05).

Unlocking the potential of forage fish to reduce the global burden of disease.

Red meat consumption is associated with an elevated risk of mortality from non-communicable diseases (NCDs). In contrast, forage fish, as highly nutritious, environmentally friendly, affordable, and the most abundant fish species in the ocean, are receiving increasing interest from a global food system perspective. However, little research has examined the impact of replacing red meat with forage fish in the global diet on diet-related NCDs. METHODS: We based our study on datasets of red meat projections in 2050 for 137 countries and forage fish catches. We replaced the red meat consumption in each country with forage fish (from marine habitats), without exceeding the potential supply of forage fish. We used a comparative risk assessment framework to investigate how such substitutions could reduce the global burden of diet-related NCDs in adults. RESULTS: The results of our study show that forage fish may replace only a fraction (approximately 8%) of the world's red meat due to its limited supply, but it may increase global daily per capita fish consumption close to the recommended level. Such a substitution could avoid 0.5-0.75 million deaths and 8-15 million disability-adjusted life years, concentrated in low- and middle-income countries. Forage fish as an alternative to red meat could double (or more) the number of deaths that could be avoided by simply reducing red meat consumption. CONCLUSIONS: Our analysis suggests that forage fish is a promising alternative to red meat. Policies targeting the allocation of forage fish to regions where they are needed, such as the Global South, could be more effective in maximising the potential of forage fish to reduce the global burden of disease.

Cost-benefit analysis of ecosystem modeling to support fisheries management.

Mathematical and statistical models underlie many of the world's most important fisheries management decisions. Since the 19th century, difficulty calibrating and fitting such models has been used to justify the selection of simple, stationary, single-species models to aid tactical fisheries management decisions. Whereas these justifications are reasonable, it is imperative that we quantify the value of different levels of model complexity for supporting fisheries management, especially given a changing climate, where old methodologies may no longer perform as well as in the past. Here we argue that cost-benefit analysis is an ideal lens to assess the value of model complexity in fisheries management. While some studies have reported the benefits of model complexity in fisheries, modeling costs are rarely considered. In the absence of cost data in the literature, we report, as a starting point, relative costs of single-species stock assessment and marine ecosystem models from two Australian organizations. We found that costs varied by two orders of magnitude, and that ecosystem model costs increased with model complexity. Using these costs, we walk through a hypothetical example of cost-benefit analysis. The demonstration is intended to catalyze the reporting of modeling costs and benefits.

MAP-box: a novel, low-cost and easy-to-fabricate 3D-printed box for the storage and transportation of dissolving microneedle array patches.

Research on the use of microarray patches (MAPs) has progressed at an unprecedented rate over the years, leading to the development of many novel drug delivery systems. As the technology approaches patients, there are several key aspects that ought to be addressed in order to facilitate the smooth translation of MAPs from bench to bedside. One integral factor includes the choice of devices and packaging for the storage of MAPs. In the current work, a slide-and-seal box, MAP-box, was developed for the storage of dissolving MAPs, using fused-deposition modelling. The device has been designed to act as a pill-box for MAPs not only to provide protection for MAPs from the environment, but also to improve patient's adherence to treatment. The overall design of the MAP-box was simple, yet offers the capability of sealing and protecting dissolving MAPs up to 30 days. Donepezil HCl was formulated into a dissolvable MAP, which was used to treat dementia related to Alzheimer's disease. This compound was used as a model formulation to evaluate the utility of the 3D printed MAP-box when placed under three storage conditions: 5 °C and ambient humidity, 25 °C and 65% relative humidity and 40 °C and 75% relative humidity. It was shown that the slide-and-seal box was able to confer protection to MAPs for up to 30 days under accelerated stability study conditions as the drug loading, mechanical properties and insertion properties of MAPs remained unaffected when compared to the unpackaged MAPs stored under these same parameters. These preliminary data provide evidence that the MAP-box prototype may be of great utility for the storage of single or multiple MAPs. Nevertheless, future work will be needed to evaluate their patient usability and its application to different types of MAP systems to fully validate the overall robustness of the prototype.

Physician Perspectives on Performing Newborn Circumcisions: Barriers and Opportunities.

OBJECTIVE: Over half of infant boys born in the United States undergo newborn circumcision. However, available data indicate that boys who are publicly insured, or Black/African American, have less access to desired newborn circumcision, thus concentrating riskier, more costly operative circumcision among these populations. This study ascertains perinatal physician perspectives about barriers and facilitators to providing newborn circumcisions, with a goal of informing future strategies to ensure more equitable access. METHODS: Qualitative interviews about newborn circumcision care were conducted from April-June 2020 at eleven Chicago-Area hospitals. Physicians that provide perinatal care (pediatricians, family medicine physicians, and obstetricians) participated in qualitative interviews about newborn circumcision. Inductive and deductive qualitative coding was performed to identify themes related to barriers and facilitators of newborn circumcision care. RESULTS: The 23 participating physicians (78% female, 74% white, median 16 years since medical school graduation [range 5-38 years], 52% hospital leadership role, 78% currently perform circumcisions) reported multiple barriers including difficulty with procedural logistics and inconsistent clinician availability and training; corresponding suggestions for operational improvements were also provided. Regarding newborn circumcision insurance coverage and reimbursement, physicians reported limited knowledge, but noted that some insurance reimbursement policies financially disincentivize clinicians and hospitals from offering inpatient newborn circumcision. CONCLUSIONS: Physicians identified logistical/operational, and reimbursement-related barriers to providing newborn circumcision for desirous families. Future studies and advocacy work should focus on developing clinical strategies and healthcare policies to ensure equitable access, and incentivize clinicians/hospitals to perform newborn circumcisions.

Evaluation of an in vitro experimental platform of human polarized intestinal epithelial monolayers for the hazard assessment of insecticidal proteins.

Previous work demonstrated the utility of using human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on Transwell® filters to differentiate between hazardous and non-hazardous proteins. The current study seeks to further resolve appropriate concentrations for evaluating proteins of unknown hazard potential using the IEC experimental platform and leverages these parameters for evaluating the potential toxicity of insecticidal proteins characteristic of those expressed in genetically modified (GM) agricultural biotechnology crops. To establish optimal test protein concentrations, effects of several known hazardous (C. perfringens epsilon toxin, Listeriolysin O, Phaseolus vulgaris erythroagglutinin, E. coli Shiga toxin 1, C. difficile Toxin B and wheat germ agglutinin) and non-hazardous (Ara-h2, ß-lactoglobulin, fibronectin and Rubisco) proteins on IEC barrier integrity and cell viability were evaluated at concentration ranges. Two insecticidal proteins (AfIP-1A and AfIP-1B) were evaluated for effects in the IEC assay, a seven-day insecticidal bioassay, and assessed in a high-dose 14-day acute oral toxicity study in mice. The results obtained from the human in vitro IEC assay were consistent with results obtained from an in vivo acute oral toxicity study, both demonstrating that the combination of AfIP-1A and AfIP-1B do not exhibit any identifiable harmful impacts on mammalian cells.

National-Scale Assessment of Total Gaseous Mercury Isotopes Across the United States.

With the 2011 promulgation of the Mercury and Air Toxics Standards by the U.S. Environmental Protection Agency, and the successful negotiation by the United Nations Environment Program of the Minamata Convention, emissions of mercury (Hg) have declined in the United States. While the declines in atmospheric Hg concentrations in North America are encouraging, linking the declines to changing domestic and global source portfolios remains challenging. To address these research gaps, the U.S. Geological Survey initiated the first national-scale effort to establish a baseline of total gaseous mercury stable isotope values at 31 sites distributed across the United States. Results indicated that unique Hg sources, such as Hg evasion from an elemental Hg contaminated site or free tropospheric intrusions in high altitude sites, were distinguishable from background atmospheric values. Minor gradients were observed across the nation, with regions of heavy industrial activity demonstrating lower δ202Hg, but no consistent changes in other isotopes such as Δ199Hg and Δ200Hg were observed. Furthermore, δ202Hg was impacted by foliar uptake and senescence but trends varied between forested regions in the northeastern and midwestern United States. These data demonstrate regional emission sources and other environmental variables can impact total gaseous Hg (TGM) isotope values, highlighting the need to characterize atmospheric Hg isotopes over larger geographical areas to evaluate changes related to national and international Hg regulations.

Differential Insurance Plan Coverage and Surgeon Reimbursement of Pediatric Circumcision at an Urban, Midwestern Hospital.

OBJECTIVE: To explore private vs public pediatric circumcision insurance coverage and surgeon reimbursement. METHODS: A telephone survey about circumcision coverage (Current Procedural Terminology codes: 54150, 54161) was conducted in October 2021 with insurance plan representatives from the 12 plans that comprised ≥1% of institutional pediatric urology visits to compare plan characteristics and coverage details. Circumcision billing data were collected at one pediatric hospital to assess surgeon reimbursement (insurance+patient payment) by plan type using bivariate statistics. RESULTS: Ten plans (5 private and 5 public) responded (83.3% response rate). All except one public plan covered newborn circumcision. For non-newborn circumcisions, most public plans (80%) had unrestricted coverage, whereas all private plans required medical necessity. Median reimbursement for newborn circumcision (CPT: 54150) was $484 for private and $78 for public plans, P < .001 while median reimbursement for non-newborn circumcision (CPT: 54161) was $314 for private and $147 for public plans, P < .001. CONCLUSION: Private insurance plans reimburse significantly more than public plans for newborn circumcision. For non-newborn circumcision, private plans reimburse more than public but the coverage is more restricted, with a smaller differential between newborn and non-newborn circumcision. This coverage and reimbursement structure may indirectly encourage newborn circumcision for privately insured boys and non-newborn circumcision for publicly insured boys.

Multi-instrument assessment of fine and ultrafine titanium dioxide aerosols.

The measurement of fine (diameter: 100 nanometers-2.5 micrometers) and ultrafine (UF: < 100 nanometers) titanium dioxide (TiO2) particles is instrument dependent. Differences in measurements exist between toxicological and field investigations for the same exposure metric such as mass, number, or surface area because of variations in instruments used, operating parameters, or particle-size measurement ranges. Without appropriate comparison, instrument measurements create a disconnect between toxicological and field investigations for a given exposure metric. Our objective was to compare a variety of instruments including multiple metrics including mass, number, and surface area (SA) concentrations for assessing different concentrations of separately aerosolized fine and UF TiO2 particles. The instruments studied were (1) DustTrak™ DRX, (2) personal DataRAMs™ (PDR), (3) GRIMMTM, and (4) diffusion charger (DC). Two devices of each field-study instrument (DRX, PDR, GRIMM, and DC) were used to measure various metrics while adjusting for gravimetric mass concentrations of fine and UF TiO2 particles in controlled chamber tests. An analysis of variance (ANOVA) was used to apportion the variance to inter-instrument (between different instrument-types), inter-device (within instrument), and intra-device components. Performance of each instrument-device was calculated using root mean squared error compared to reference methods: close-faced cassette and gravimetric analysis for mass and scanning mobility particle sizer (SMPS) real-time monitoring for number and SA concentrations. Generally, inter-instrument variability accounted for the greatest (62.6% or more) source of variance for mass, and SA-based concentrations of fine and UF TiO2 particles. However, higher intra-device variability (53.7%) was observed for number concentrations measurements with fine particles compared to inter-instrument variability (40.8%). Inter-device variance range(0.5-5.5%) was similar for all exposure metrics. DRX performed better in measuring mass closer to gravimetric than PDRs for fine and UF TiO2. Number concentrations measured by GRIMMs and SA measurements by DCs were considerably (40.8-86.9%) different from the reference (SMPS) method for comparable size ranges of fine and UF TiO2. This information may serve to aid in interpreting assessments in risk models, epidemiologic studies, and development of occupational exposure limits, relating to health effect endpoints identified in toxicological studies considering similar instruments evaluated in this study.

Assessment of worker chemical exposures in California vape shops.

E-cigarettes are battery-operated devices that heat a liquid mixture to make an aerosol that is inhaled, or vaped, by the user. Vape shops are retail environments designed to fulfill customer demand for diverse e-liquid flavors and hardware options, which create unique worker exposure concerns. To characterize exposures to vape shop workers, especially to flavoring chemicals associated with known respiratory toxicity, this study recruited vape shops from the San Francisco Bay Area. In six shops, we measured air concentrations for volatile organic compounds, formaldehyde, flavoring chemicals, and nicotine in personal and/or area samples; analyzed components of e-liquids vaped during field visits; and assessed metals on surface wipe samples. Interviews and observations were conducted over the course of a workday in the same six shops and interviews were performed in an additional six where sampling was not conducted. Detections of the alpha-diketone butter flavoring chemicals diacetyl and/or 2,3-pentanedione were common: in the headspace of purchased e-liquids (18 of 26 samples), in personal air samples (5 of 16), and in area air samples (2 of 6 shops). Two exceedances of recommended exposure limits for 2,3-pentanedione (a short-term exposure limit and an 8-hr time-weighted average) were measured in personal air samples. Other compounds detected in the area and personal air samples included substitutes for diacetyl and 2,3-pentanedione (acetoin and 2,3-hexanedione) and compounds that may be contaminants or impurities. Furthermore, a large variety (82) of other flavoring chemicals were detected in area air samples. None of the 12 shops interviewed had a health and safety program. Six shops reported no use of any personal protective equipment (PPE) (e.g., gloves, chemical resistant aprons, eye protection) and the others stated occasional use; however, no PPE use was observed during any field investigation day. Recommendations were provided to shops that included making improvements to ventilation, hygiene, use of personal protective equipment, and, if possible, avoidance of products containing the alpha-diketone flavoring chemicals. Future research is needed to evaluate the long-term health risks among workers in the vape shop retail industry and for e-cigarette use generally. Specific areas include further characterizing e-liquid constituents and emissions, evaluating ingredient health risks, evaluating the contributions of different routes of exposure (dermal, inhalation, and ingestion), and determining effective exposure mitigation measures.

Neonatal circumcision availability in the United States: a physician survey.

BACKGROUND: A significant proportion of boys present to surgical specialists later in infancy/early childhood for elective operative circumcision despite the higher procedural risks. This study aims to assess physician perspectives on access to neonatal circumcision across the United States and identify potential reasons contributing to disparities in access. METHODS: A cross-sectional survey was electronically distributed to physician members of the Societies for Pediatric Urology and the American Academy of Pediatrics Section on Hospital Medicine. Hospital characteristics and circumcision practices were assessed. Associations between NC availability and institutional characteristics were evaluated using chi-squared testing and multivariable logistic regression. Qualitative analyses of free-text comments were performed. RESULTS: A total of 367 physicians responded (129 urologists [41%], 188 pediatric hospitalists [59%]). Neonatal circumcision was available at 86% of hospitals represented. On univariate and multivariate analysis, the 50 hospitals that did not offer neonatal circumcision were more likely to be located in the Western region (odds ratio [OR] = 8.33; 95% confidence interval [CI] 3.1-25 vs. Midwest) and in an urban area (OR = 4.2; 95% CI 1.6-10 vs. suburban/rural) compared with hospitals that offered neonatal circumcision. Most common reasons for lack of availability included not a birth hospital (N = 22, 47%), lack of insurance coverage (N = 8, 17%), and low insurance reimbursement (N = 7, 15%). Institutional, regional, or provider availability (68%), insurance/payment (12.4%), and ethics (12.4%) were common themes in the qualitative comments. CONCLUSIONS: Overall availability of neonatal circumcision varied based on hospital characteristics, including geography. Information from this survey will inform development of interventions designed to offer neonatal circumcision equitably and comprehensively.

A National Survey of Wilderness Medicine Curricula in United States Emergency Medicine Residencies.

INTRODUCTION: Wilderness medicine (WM) is a growing subspecialty of emergency medicine. In 2018, we surveyed all 240 emergency medicine residencies in the United States to assess the scope of WM education in emergency medicine training programs in light of the nearly 30% increase in the number of residencies since 2015. METHODS: A survey was e-mailed to the Council of Residency Directors in Emergency Medicine listserv and individual program directors of each of the 240 residencies. The survey included questions on educational content, format, number of hours taught, availability of conference credit, offering of an elective or fellowship, and several predefined WM curricula. We evaluated differences between 3-y and 4-y residencies using the χ2 test, where P<0.05 was considered significant. RESULTS: We had a response rate of 57% for completed surveys. Analysis showed 63% of respondent programs teach WM material. The majority (86%) partially or completely developed their curriculum, with 33% offering at least 1 of the predefined curricula. Thirteen percent taught with lecture only, 2% taught by hands-on only, and 85% used a combination of the 2. WM electives were significantly more likely to be offered by 4-y than 3-y residencies (P=0.009). CONCLUSIONS: Almost two-thirds of respondent residency programs teach WM material. Of these, only one-third teach any of the predefined curricula. Four-year residencies are more likely to offer WM electives but are otherwise comparable to 3-y programs.

Correlations Between Retinal Optical Coherence Tomography and Histopathology in Preclinical Safety Assessment of Ocular Therapies.

METHODS: Twelve studies that involved intravitreal or subretinal test article administration in multiple laboratory animal species and employed both OCT and histopathologic assessment were identified. These data were compared to determine the degree of correlation for each identified abnormality. RESULTS: Severity of observed OCT and histopathological changes ranged from minimal to severe, with moderate and severe changes having a higher rate of agreement between the 2 techniques. Changes to well-defined structures, including the retinal blood vessels, optic nerve, and retinal pigment epithelium, also showed a strong correlation. CONCLUSIONS: There was a strong correlation between OCT and histopathology in both intravitreal and subretinal injection studies, demonstrating the value of collaboration between the study ophthalmologist and pathologist and offering translatable means to monitor pharmacological or toxicological effects in preclinical toxicological studies.

Self-equity as a trustworthiness measure: The relationship among self-equity and security clearance eligibility adjudications in US Army recruits.

The United States government's clearance adjudication process examines past behavior to determine soldier eligibility for a security clearance. For young recruits with a short-documented history, however, little information is available. While informal social controls generally associate with criminal desistance, desistance speaks little about those who have yet to offend. This work extends informal social control theory to better understand military clearance eligibility adjudication outcomes as measured in terms of a self-equity construct. This analysis looks at a twelve-year cohort of US Army recruits who received clearance eligibility adjudication within the first five years of service, as recorded in military archival data in the Person-event Data Environment (PDE) database. Laub, Rowan, & Sampson's (2018) age-graded theory of informal social control is tested to estimate models, capturing the self-equity effects of moral waiver, qualification-test percentiles, service time, rank, education, and childbirth-marriage interaction. The results demonstrate that self-equity substantively relates to security clearance eligibility adjudication outcomes. These findings carry policy implications for the creation of an objective trustworthiness measure in the absence of reliable documented history.

Development, Evaluation, and Pharmacokinetic Assessment of Polymeric Microarray Patches for Transdermal Delivery of Vancomycin Hydrochloride.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause harmful and potentially deadly infections. Vancomycin remains the first-line antibiotic treatment for MRSA-derived infections. Nevertheless, as a peptide drug, it is poorly absorbed when administered orally because of its high molecular weight and low permeability in the gastrointestinal tract and is therefore administered intravenously for the treatment of systemic diseases. In order to circumvent some of the many drawbacks associated with intravenous injection, other routes of drug delivery should be investigated. One of the strategies which has been employed to enhance transdermal drug delivery is based on microarray patches (MAPs). This work, for the first time, describes successful transdermal delivery of vancomycin hydrochloride (VCL) using dissolving MAPs (DMAPs) and hydrogel-forming MAPs (HFMAPs). VCL was formulated into DMAPs and reservoirs [film dosage forms, lyophilized wafers, and compressed tablets (CSTs)] using excipients such as poly(vinyl pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, d-sorbitol, and glycerol. In this study, HFMAPs were manufactured using aqueous blends containing poly(methylvinyl ether-co-maleic acid) cross-linked by esterification with poly(ethylene glycol). The VCL-loaded CSTs (60% w/w VCL) were the most promising reservoirs to be integrated with HFMAPs based on the physicochemical evaluations performed. Both HFMAPs and DMAPs successfully delivered VCL in ex vivo studies with the percentage of drug that permeated across the neonatal porcine skin recorded at 46.39 ± 8.04 and 7.99 ± 0.98%, respectively. In in vivo studies, the area under the plasma concentration time curve from time zero to infinity (AUC0-∞) values of 162.04 ± 61.84 and 61.01 ± 28.50 µg h/mL were achieved following the application of HFMAPs and DMAPs, respectively. In comparison, the AUC0-∞ of HFMAPs was significantly greater than that of the oral administration control group, which showed an AUC0-∞ of 30.50 ± 9.18 µg h/mL (p < 0.05). This work demonstrates that transdermal delivery of VCL is feasible using DMAPs and HFMAPs and could prove effective in the treatment of infectious diseases caused by MRSA, such as skin and soft tissue infections, lymphatic-related infections, and neonatal sepsis.

A Drug Content, Stability Analysis, and Qualitative Assessment of Pharmacists' Opinions of Two Exemplar Extemporaneous Formulations.

Despite a decline in the number of active pharmaceutical ingredients prepared extemporaneously using proprietary products, there remains a need for such products in the community (for example, liquid medicines for paediatrics which may be otherwise commercially unavailable). A lack of experience and quality assurance systems may have diminished pharmacist's confidence in the extemporaneous preparation process; therefore, pharmacists were asked to prepare two proprietary products, omeprazole and amlodipine. The resulting products were characterised in terms of variability in drug quantity, stability, particle size and antimicrobial properties. Furthermore, a self-administered questionnaire was used to assess 10 pharmacists' opinions on the perceived complexity of the extemporaneous compounding process and their overall confidence in the final extemporaneously compounded products. Drug content studies revealed that 88.5% and 98.0% of the desired drug content was obtained for omeprazole and amlodipine, respectively. Antimicrobial properties were maintained for both drugs, however variability in particle size, particularly for amlodipine, was evident between formulations. While pharmacists who partook in the study had some or high confidence in the final products, they reported difficulty formulating the suspensions. Findings from this study provide insight into pharmacists' views on two extemporaneously prepared products and highlight the variability obtained in preparations prepared by different pharmacists.

Current Concepts in the Epidemiology, Diagnosis, and Management of Histoplasmosis Syndromes.

Histoplasmosis is a global disease endemic to regions of all six inhabited continents. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. As a result of climate change and anthropogenic land utilization, the conditions suitable for Histoplasma capsulatum are changing, leading to a corresponding change in epidemiology. The clinical manifestations of histoplasmosis are protean, variably resembling other common conditions such as community-acquired pneumonia, tuberculosis, sarcoidosis, Crohn's disease, or malignancy. Making a successful diagnosis is contingent on a thorough understanding of epidemiology, common clinical presentations, and best testing practices for histoplasmosis. While most subclinical or self-limited diseases do not require treatment in immunocompetent patients, all immunocompromised patients and those with progressive disseminated disease or chronic pulmonary disease should be treated. Liposomal amphotericin B is the preferred agent for severe or disseminated disease, while itraconazole is adequate for milder cases and "step-down" therapy following response to amphotericin B. In this review, we discuss the current evidence-based approaches to the epidemiology, diagnosis, and management of histoplasmosis.

Peaks, Means, and Determinants of Real-Time TVOC Exposures Associated with Cleaning and Disinfecting Tasks in Healthcare Settings.

Cleaning and disinfecting tasks and product use are associated with elevated prevalence of asthma and respiratory symptoms among healthcare workers; however, the levels of exposure that pose a health risk remain unclear. The objective of this study was to estimate the peak, average, and determinants of real-time total volatile organic compound (TVOC) exposure associated with cleaning tasks and product-use. TVOC exposures were measured using monitors equipped with a photoionization detector (PID). A simple correction factor was applied to the real-time measurements, calculated as a ratio of the full-shift average TVOC concentrations from a time-integrated canister and the PID sample, for each sample pair. During sampling, auxiliary information, e.g. tasks, products used, engineering controls, was recorded on standardized data collection forms at 5-min intervals. Five-minute averaged air measurements (n = 10 276) from 129 time-series comprising 92 workers and four hospitals were used to model the determinants of exposures. The statistical model simultaneously accounted for censored data and non-stationary autocorrelation and was fit using Markov-Chain Monte Carlo within a Bayesian context. Log-transformed corrected concentrations (cTVOC) were modeled, with the fixed-effects of tasks and covariates, that were systematically gathered during sampling, and random effect of person-day. The model-predicted geometric mean (GM) cTVOC concentrations ranged from 387 parts per billion (ppb) for the task of using a product containing formaldehyde in laboratories to 2091 ppb for the task of using skin wipes containing quaternary ammonium compounds, with a GM of 925 ppb when no products were used. Peak exposures quantified as the 95th percentile of 15-min averages for these tasks ranged from 3172 to 17 360 ppb. Peak and GM task exposures varied by occupation and hospital unit. In the multiple regression model, use of sprays was associated with increasing exposures, while presence of local exhaust ventilation, large room volume, and automatic sterilizer use were associated with decreasing exposures. A detailed understanding of factors affecting TVOC exposure can inform targeted interventions to reduce exposures and can be used in epidemiologic studies as metrics of short-duration peak exposures.