Mark Albrecht

Forced-air warming blowers: An evaluation of filtration adequacy and airborne contamination emissions in the operating room.

BACKGROUND Forced-air warming (FAW) is widely used to prevent hypothermia during surgical procedures. The airflow from these blowers is often vented near the operative site and should be free of contaminants to minimize the risk of surgical site infection. Popular FAW blowers contain a 0.2-μm rated intake filter to reduce these risks. However, there is little evidence that the efficiency of the intake filter is adequate to prevent airborne contamination emissions or protect the internal air path from microbial contamination buildup. METHODS Five new intake filters were obtained directly from the manufacturer (Bair Hugger 505, model 200708D; Arizant Healthcare, Eden Prairie, MN), and 5 model 200708C filters currently in hospital use were removed from FAW devices. The retention efficiency of these filters was assessed using a monodisperse sodium chloride aerosol. In the same hospitals, internal air path surface swabs and hose outlet particle counts were performed on 52 forced-air warming devices (all with the model 200708C filter) to assess internal microbial buildup and airborne contamination emissions. RESULTS Intake filter retention efficiency at 0.2 μm was 93.8% for the 200708C filter and 61.3% at for the 200708D filter. The 200708D filter obtained directly from the manufacturer has a thinner filtration media than the 200708C filter in current hospital use, suggesting that the observed differences in retention efficiency were due to design changes. Fifty-eight percent of the FAW blowers evaluated were internally generating and emitting airborne contaminants, with microorganisms detected on the internal air path surfaces of 92.3% of these blowers. Isolates of Staphylococcus aureus, coagulase-negative Staphylococcus, and methicillin-resistant S aureus were detected in 13.5%, 3.9%, and 1.9% of FAW blowers, respectively. CONCLUSION The design of popular FAW devices using the 200708C filter was found to be inadequate for preventing the internal buildup and emission of microbial contaminants into the operating room. Substandard intake filtration allowed airborne contaminants (both viable and nonviable) to penetrate the intake filter and reversibly attach to the internal surfaces within the FAW blowers. The reintroduction of these contaminants into the FAW blower air stream was detected and could contribute to the risk of cross-infection. Given the deficiencies identified with the 200708C intake filter, the introduction of a new filter (model 200708D) with substantially lower retention efficiency is of concern.

Forced-air warming: a source of airborne contamination in the operating room?

Forced-air-warming (FAW) is an effective and widely used means for maintaining surgical normothermia, but FAW also has the potential to generate and mobilize airborne contamination in the operating room. We measured the emission of viable and non-viable forms of airborne contamination from an arbitrary selection of FAW blowers (n=25) in the operating room. A laser particle counter measured particulate concentrations of the air near the intake filter and in the distal hose airstream. Filtration efficiency was calculated as the reduction in particulate concentration in the distal hose airstream relative to that of the intake. Microbial colonization of the FAW blowers internal hose surfaces was assessed by culturing the microorganisms recovered through swabbing (n=17) and rinsing (n=9) techniques. Particle counting revealed that 24% of FAW blowers were emitting significant levels of internally generated airborne contamination in the 0.5 to 5.0 µm size range, evidenced by a steep decrease in FAW blower filtration efficiency for particles 0.5 to 5.0 µm in size. The particle size-range-specific reduction in efficiency could not be explained by the filtration properties of the intake filter. Instead, the reduction was found to be caused by size-range-specific particle generation within the FAW blowers. Microorganisms were detected on the internal air path surfaces of 94% of FAW blowers. The design of FAW blowers was found to be questionable for preventing the build-up of internal contamination and the emission of airborne contamination into the operating room. Although we did not evaluate the link between FAW and surgical site infection rates, a significant percentage of FAW blowers with positive microbial cultures were emitting internally generated airborne contamination within the size range of free floating bacteria and fungi (<4 µm) that could, conceivably, settle onto the surgical site.

Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations

Chronic lymphocytic leukemia (CLL) displays remarkable ethnic predisposition for whites, with relative sparing of African-American and Asian populations. In addition, CLL displays among the highest familial predispositions of all hematologic malignancies, yet the genetic basis for these differences is not clearly defined. The highly polymorphic HLA genes of the major histocompatibility complex play a central role in immune surveillance and confer risk for autoimmune and infectious diseases and several different cancers, the role for which in the development of CLL has not been extensively investigated. The National Marrow Donor Program/Be The Match has collected HLA typing from CLL patients in need of allogeneic hematopoietic stem cell transplant and has recruited millions of volunteers to potentially donate hematopoietic stem cells. HLA genotypes for 3491 US white, 397 African-American, and 90 Hispanic CLL patients were compared with 50 000 controls per population from the donor registry. We identified several HLA alleles associated with CLL susceptibility in each population, reconfirming predisposing roles of HLA-A*02:01 and HLA-DRB4*01:01 in whites. Associations for haplotype DRB4*01:01∼DRB1*07:01∼DQB1*03:03 were replicated across all 3 populations. These findings provide a comprehensive assessment of the role of HLA in the development of severe CLL.

Patient warming excess heat: The effects on orthopedic operating room ventilation performance

BACKGROUND: Patient warming has become a standard of care for the prevention of unintentional hypothermia based on benefits established in general surgery. However, these benefits may not fully translate to contamination-sensitive surgery (i.e., implants), because patient warming devices release excess heat that may disrupt the intended ceiling-to-floor ventilation airflows and expose the surgical site to added contamination. Therefore, we studied the effects of 2 popular patient warming technologies, forced air and conductive fabric, versus control conditions on ventilation performance in an orthopedic operating room with a mannequin draped for total knee replacement. METHODS: Ventilation performance was assessed by releasing neutrally buoyant detergent bubbles (“bubbles”) into the nonsterile region under the head-side of the anesthesia drape. We then tracked whether the excess heat from upper body patient warming mobilized the “bubbles” into the surgical site. Formally, a randomized replicated design assessed the effect of device (forced air, conductive fabric, control) and anesthesia drape height (low-drape, high-drape) on the number of bubbles photographed over the surgical site. RESULTS: The direct mass-flow exhaust from forced air warming generated hot air convection currents that mobilized bubbles over the anesthesia drape and into the surgical site, resulting in a significant increase in bubble counts for the factor of patient warming device (P < 0.001). Forced air had an average count of 132.5 versus 0.48 for conductive fabric (P = 0.003) and 0.01 for control conditions (P = 0.008) across both drape heights. Differences in average bubble counts across both drape heights were insignificant between conductive fabric and control conditions (P = 0.87). The factor of drape height had no significant effect (P = 0.94) on bubble counts. CONCLUSIONS: Excess heat from forced air warming resulted in the disruption of ventilation airflows over the surgical site, whereas conductive patient warming devices had no noticeable effect on ventilation airflows. These findings warrant future research into the effects of forced air warming excess heat on clinical outcomes during contamination-sensitive surgery.

Efficacy of a novel air filtration pillow for avoidance of perennial allergens in symptomatic adults

BACKGROUND Nighttime allergen exposures are a primary contributor to the development of allergic and asthmatic morbidities. Disease management guidelines recommend the use of environmental control measures to reduce these exposures, but clinically relevant reductions are difficult to achieve because most measures control only 1 allergen source among many in the bedroom environment. OBJECTIVE To determine whether a novel localized approach to nighttime allergen avoidance provides effective exposure reductions and clinical benefits. METHODS Thirty-five adults with perennial allergic rhinoconjunctivitis (dog, cat, or dust mite sensitivity) were randomized to receive PureZone, a combination therapy involving localized air filtration and pillow encasement, or placebo in a crossover trial with two 2-week treatment periods separated by a 1-week washout. Nasal and ocular allergy symptoms, quality of life, and breathing zone particulate exposure were assessed. Bedroom allergen dust samples were collected in the sleeping environment. RESULTS Reductions (>99.99%) in allergen-sized particulate (> or = 0.3 microm) in the breathing zone led to significant improvements in nocturnal nasal and ocular allergy symptoms (P < .001) and quality of life (P = .02) for the active vs placebo device. Significant nocturnal symptom reductions vs placebo occurred the second night of use and were maintained for the duration of treatment; these reductions improved sleep problems in particular (P = .02). Allergens were detected in 100% of bedrooms, of which 44% had levels that exceeded sensitizing thresholds. CONCLUSIONS The combination therapy of pillow encasement and localized air filtration provided effective nighttime allergen exposure reductions and clinical benefits without the use of adjunctive therapy.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

Conjoint analysis and discrete choice experiments for quality improvement

Conjoint analysis and discrete choice experiments, which were developed in fields such as marketing and economics, are useful for understanding the voice of the customer to guide quality-improvement efforts. Unfortunately, these methods have received relatively little attention in the quality area. In this article, we provide some guidelines for the use of conjoint analysis and discrete choice experiments. We discuss what they are, why they are useful methodologies for quality improvement, and how a discrete choice experiment can be carried out. We demonstrate the methodology by discussing a real case study in quality improvement in detail. We then introduce a new class of designs for discrete choice experiments that are robust for a class of possible models. We provide several examples in which an optimal design based on the main-effects only models is shown to have limited capability for estimation of two-factor interactions, whereas the proposed robust designs perform well in the presence of two-factor interactions. We conclude with a summary of key points and directions for future research.

Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program.

Measures of allele and haplotype diversity, which are fundamental properties in population genetics, often follow heavy tailed distributions. These measures are of particular interest in the field of hematopoietic stem cell transplant (HSCT). Donor/Recipient suitability for HSCT is determined by Human Leukocyte Antigen (HLA) similarity. Match predictions rely upon a precise description of HLA diversity, yet classical estimates are inaccurate given the heavy-tailed nature of the distribution. This directly affects HSCT matching and diversity measures in broader fields such as species richness. We, therefore, have developed a power-law based estimator to measure allele and haplotype diversity that accommodates heavy tails using the concepts of regular variation and occupancy distributions. Application of our estimator to 6.59 million donors in the Be The Match Registry revealed that haplotypes follow a heavy tail distribution across all ethnicities: for example, 44.65% of the European American haplotypes are represented by only 1 individual. Indeed, our discovery rate of all U.S. European American haplotypes is estimated at 23.45% based upon sampling 3.97% of the population, leaving a large number of unobserved haplotypes. Population coverage, however, is much higher at 99.4% given that 90% of European Americans carry one of the 4.5% most frequent haplotypes. Alleles were found to be less diverse suggesting the current registry represents most alleles in the population. Thus, for HSCT registries, haplotype discovery will remain high with continued recruitment to a very deep level of sampling, but population coverage will not. Finally, we compared the convergence of our power-law versus classical diversity estimators such as Capture recapture, Chao, ACE and Jackknife methods. When fit to the haplotype data, our estimator displayed favorable properties in terms of convergence (with respect to sampling depth) and accuracy (with respect to diversity estimates). This suggests that power-law based estimators offer a valid alternative to classical diversity estimators and may have broad applicability in the field of population genetics.

HLA polymorphism and risk of multiple myeloma.

CF; when no methodology modifications were introduced since the time of the last calibration, we obtained highly concordant CFs (Supplementary Table 6). For appropriate clinical decisions, we need to judge agreement between the methods after IS conversion; to this aim, we interchanged 41 whole blood samples (divided into two parts) from CML patients with Lab#09. The concordance in MR between the reference method and the external laboratory was 88% after conversion (36 out of 41 samples were in the same MR category) (Figure 2c). This result underlines the importance of conversion to the IS, given that after harmonization we were able to halve the number of discordant data (from nine to five cases). In the present study, we show that secondary reference biological calibrators anchored to the WHO primary standards can decrease inter-laboratory variability. Our results, together with those recently reported by Cross et al., substantiate the objective initially set during the establishment of the WHO primary standards, that is, to facilitate worldwide diffusion of the IS. For the first time in Latin America, this study provides a platform on which to assess the performance of distinct clinical BCR-ABL1 tests and confirm the utility of secondary reference materials to further improve IS accuracy and inter-laboratory precision. This effort will continue in the future by providing secondary reference material to the centers involved in this project and potential new participants; moreover, due to its higher precision and absolute quantification capability, we are evaluating the possibility of including digital PCR as the calibration method for the future.

Asymmetric linkage disequilibrium: Tools for assessing multiallelic LD

Standard measures of linkage disequilibrium (LD) provide an incomplete description of the correlation between two loci. Recently, Thomson and Single (2014) described a new asymmetric pair of LD measures (ALD) that give a more complete description of LD. The ALD measures are symmetric and equivalent to the correlation coefficient r when both loci are bi-allelic. When the numbers of alleles at the two loci differ, the ALD measures capture this asymmetry and provide additional detail about the LD structure. In disease association studies the ALD measures are useful for identifying additional disease genes in a genetic region, by conditioning on known effects. In evolutionary genetic studies ALD measures provide insight into selection acting on individual amino acids of specific genes, or other loci in high LD (see Thomson and Single (2014) for these examples). Here we describe new software for computing and visualizing ALD. We demonstrate the utility of this software using haplotype frequency data from the National Marrow Donor Program (NMDP). This enhances our understanding of LD patterns in the NMDP data by quantifying the degree to which LD is asymmetric and also quantifies this effect for individual alleles.