Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

BACKGROUND: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. OBJECTIVE: Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. METHODS: To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. RESULTS: Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. CONCLUSIONS: This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64446.

Quality Gap in Long-Stay Antipsychotic Quality Measure Performance Widens Over the Pandemic, Reversing Past Gains.

The Centers for Medicare & Medicaid Services (CMS) grades nursing home performance in antipsychotic prescribing quarterly, publishing findings as a quality measure. While scores have improved since 2011, marked performance variation between facilities persists. To assess quality gap changes between best- and worst-performing deciles, we compared quarterly prescribing changes between these groups pre-pandemic (April 2011 to March 2020) and during the pandemic (April 2020 to March 2022). Antipsychotic quality measure scores, improving pre-pandemic, deteriorated during the pandemic. The pre-pandemic quality gap between the best- and worst-performing deciles narrowed as the worst-performing decile improved faster than the best-performing decile. During the pandemic, the quality gap widened as the worst-performing decile relapsed more than the best-performing decile (p < .0001). The pandemic disrupted quality performance gains and compounded disparities between facilities. A better understanding of the factors allowing high performers to weather pandemic stressors better than poor performers may reveal opportunities to improve nursing home quality and equity for all residents.

Changes in the Radiology Practice Landscape and Indicators of Practice Consolidation From 2014 to 2023.

BACKGROUND. A range of economic and health policy incentives are leading to ongoing consolidation among payers, hospitals, and physician practices. OBJECTIVE. The purpose of the present study was to evaluate consolidation among radiologists' affiliated practices through 2023, analyze the impact of consolidation on such practices' specialty mix and size, and assess radiologists' new affiliations after prior practices cease. METHODS. CMS data from 2014 to 2023 were used to identify all radiologists nationally along with their affiliated practices. Based on the specialty mix of all affiliated physicians, practices were categorized as radiology only or multispecialty; multispecialty practices were further categorized as radiology majority, other specialty majority, or no majority specialty. Practices that ceased (i.e., became absent within CMS data) were identified. Temporal shifts were assessed to infer consolidation patterns. RESULTS. From 2014 to 2023, the number of radiologists enrolled in Medicare increased 17.3% (from 30,723 to 36,024), whereas the number of affiliated practices decreased 14.7% (from 5059 to 4313). The number of radiology-only, radiology-majority, other-specialty-majority, and no-majority-specialty practices changed by -31.8% (from 3104 to 2118), 10.9% (from 402 to 446), -5.7% (from 615 to 580), and 24.6% (from 938 to 1169), respectively. The number of practices with one to two, three to nine, 10-24, 25-49, 50-99, and 100 or more radiologists changed by -18.7% (from 2233 to 1815), -34.4% (from 1406 to 923), -25.2% (from 910 to 681), 33.2% (from 352 to 469), 121.6% (from 125 to 277), and 348.5% (from 33 to 148). A total of 3494 practices ceased, including 2281 radiology-only practices. Among 3854 radiologists whose only affiliation was a ceased radiology-only practice, their subsequent-year affiliation was a radiology-only practice in 54.3% and a multispecialty practice type in the remaining instances. CONCLUSION. An overall decrease in the number of radiology practices and concurrent growth in the number of radiologists was mirrored by shifts from small toward large practices and from radiology-only toward multispecialty practices, consistent with ongoing practice consolidation. Although determining the causes of consolidation was beyond this scope of this study, the shifts may relate to economic incentives and legislative changes favoring large multispecialty practices. CLINICAL IMPACT. The continued consolidation of radiologists into large multispecialty practices may facilitate subspecialization and greater negotiating power in payer contracting. However, radiologists may prefer smaller and/or radiology-only practices for reasons of autonomy and influence on practice structure.

Radiologists' 2021 Quality Reporting and Performance in Medicare's Merit-Based Incentive Payment System: Analysis by Practice Type.

This study of national CMS data shows differences in quality reporting and performance of Merit-Based Incentive Payment System (MIPS)-participating radiologists by practice specialty mix. For certain practice types, radiologist-reported quality measures were commonly not radiology measures. The results support a need to expand radiology measures and to better align measure reporting with clinician specialty.

Family Practices in Transforming Clinical Practice Initiative Showed No Changes in Medicare Costs or Utilization.

BACKGROUND: The Centers for Medicare and Medicaid Services proposed that the Transforming Clinical Practice Initiative (TCPI) would improve health outcomes for patients, reduce utilization of institutional services, and generate significant savings for payers by the end of September 2019. OBJECTIVE: The objective of this study was to investigate whether participation in TCPI's Practice Transformation Networks (PTNs) was associated with improved cost and utilization outcomes for Medicare patients of family medicine-based practices in the first 2 years, that is, 2016-2017, of the Initiative. STUDY DESIGN: A quasi-experimental design with a longitudinal cohort of family medicine-based practices and a propensity-matched comparison sample. SUBJECTS: A total of 761 PTN practices and 3451 non-PTN practices. MEASURES: To measure practice-level patient outcomes, we attributed patients to practice based on the plurality of office visits. We obtained Medicare claims from 2011 to 2017 to assess PTN participation effects for Medicare Part A and B costs, hospital admission, and emergency department visit rates using a Difference-in-Differences design, adjusting for baseline characteristics. RESULTS: The differences in Medicare Part A and B costs (-1.71%, P=0.25), annual rates of hospitalization (-0.59%, P=0.12) and emergency department visit (-0.29%, P=0.46) were not significantly lower among PTN practices (N=761) than among propensity score-matched non-PTN practices (N=3541). CONCLUSIONS: TCPI's transforming efforts, such as the outcomes examined in the study, might need a longer time frame to manifest and require evaluation after the full 4-year participation period. The indistinguishable effect of PTN participation may also be attributed to the fact that non-PTN practices might have participated in other initiatives that changed their care and curbed health care utilization and costs consequently.

Measuring State-Level Racial Inequity in Severe Maternal Morbidity in the Medicaid Population.

OBJECTIVE: Severe maternal morbidity represents a "near miss" mortality and is an important measure of quality and safety. Racial inequity in maternal morbidity is stark and the reasons for this disparity are poorly understood. We aimed to identify states achieving racial equity in maternal morbidity in order to identify policies that may promote racial equity. METHODS: We analyzed Medicaid deliveries from 2008 to 2009 in a sample that included 28 states and the District of Columbia. This dataset included approximately 80% of all Medicaid enrollees and 90% of minority Medicaid enrollees in the US. We determined the Non-Hispanic Black/Non-Hispanic white SMMI rate ratio for each state and categorized the states into groups by rate ratio. We described demographic features of both the general population and study population for these groups of states. RESULTS: In a sample that included a total of 1,489,134 births, we found that no state/district is achieving equity in severe maternal morbidity. The severe maternal morbidity rate is higher for Non-Hispanic Black than Non-Hispanic white patients in every state included. With a rate ratio ranging from 1.14 to 2.66, there are varying degrees of inequity. States in the group with the most equitable maternal morbidity rates had less inequity across racial subgroups with respect to educational attainment and poverty. CONCLUSIONS: Identifying geographic areas with varying degrees of inequity may be key to identifying policies to promote equity. Socioecological disparities and inadequate access to care may be factors in racial inequity in maternal morbidity.

Medicare Support for Dental and Podiatry Graduate Medical Education Programs.

Importance: Oral health care faces ongoing workforce challenges that affect patient access and outcomes. While the Medicare program provides an estimated $14.6 billion annually in graduate medical education (GME) payments to teaching hospitals, including explicit support for dental and podiatry programs, little is known about the level or distribution of this public investment in the oral health and podiatry workforce. Objective: To examine Medicare GME payments to teaching hospitals for dental and podiatry residents from 1998 to 2018, as well as the distribution of federal support among states, territories, and the District of Columbia. Design, Setting, and Participants: This cross-sectional study was conducted using data from 1252 US teaching hospitals. Data were analyzed from May through August 2020. Exposures: Dental and podiatry residency training. Main Outcomes and Measures: Medicare dental and podiatry GME payments were examined. Results: Among 1252 teaching hospitals, Medicare provided nearly $730 million in dental and podiatry GME payments in 2018. From 1998 to 2018, the number of residents supported more than doubled, increasing from 2340 residents to 4856 residents, for a 2.1-fold increase, while Medicare payments for dental and podiatry GME increased from $279 950 531 to $729 277 090, for a 2.6-fold increase. In 2018, an estimated 3504 of 4856 supported positions (72.2%) were dental. Medicare GME payments varied widely among states, territories, and the District of Columbia, with per capita payments by state, territory, and district population ranging from $0.05 in Puerto Rico to $14.24 in New York, while 6 states received no support for dental or podiatry residency programs. Conclusions and Relevance: These findings suggest that dental and podiatry GME represents a substantial public investment, and deliberate policy decisions are needed to target this nearly $730 million and growing investment to address the nation's priority oral and podiatry health needs.

Primary Care Physician Characteristics Associated with Prescribing Potentially Inappropriate Medication for Elderly Patients: Medicare Part D Data.

BACKGROUND: Despite the high risk of adverse drug events associated with potentially inappropriate medications (PIMs), primary care physicians (PCPs) continue to prescribe them for the elderly. The objective of this study was to explore PIM prescribing behavior in relation to characteristics among PCPs practicing in the United States. METHODS: We conducted a retrospective cohort study of PCPs in the 2013 to 2015 Medicare Part D Public Use File. We obtained physician characteristics from the 2015 American Medical Association (AMA) Masterfile. For each PCP, we calculated the ratio of primary care-relevant PIM claims to all drug claims (PIM rate) based on Beers Criteria. We used a multivariate regression model to assess the associations between physician characteristics and PIM rate. RESULTS: The study sample contained 111,461 PCPs who specialized in family medicine, internal medicine, general practice and geriatric medicine. Although the mean PIM rate was low at 4.9%, it varied widely across PCPs with the bottom quartile at 1.2% and the top quartile at 10.1%. PCPs in the top quartile were on average older, more likely to be male, have a DO degree, practice in the South, and have a smaller Medicare patient panel. A multivariate analysis confirmed that even after adjusting for patient panel characteristics, physician characteristics including gender, age, professional degree, specialty, practice location, practice size, and patient panel size were associated with PIM rate. CONCLUSION: Identifying PCPs with higher PIM rates can guide future interventions to increase safe prescribing for elderly populations.

Accountable Care Organizations Serving Deprived Communities Are Less Likely to Share in Savings.

PURPOSE: Primary care physicians are increasingly participating in accountable care organizations (ACOs). While prior studies have identified ACO and patient characteristics associated with savings, none have examined characteristics of the communities served by ACOs. Our objective was to assess the relationship between an ACO's service area characteristics and its savings rate. METHODS: In this cross-sectional study, we used the Centers for Medicare and Medicaid Services 2014 Medicare Shared Savings Program ACO Provider and Beneficiary, and Public Use Files to identify ACO and beneficiary characteristics. We used the American Community Survey to measure community deprivation at the ACO service area-level by using the social deprivation index. The outcome of interest was the ACO savings rate. We conducted bivariate analyses and regressions, adjusting for ACO organization and beneficiary characteristics. RESULTS: Our sample consisted of 320 ACOs participating in the Shared Savings Plan. The savings rate for ACOs serving the most deprived communities was 1.19% compared with 1.14% for those serving the least deprived. Adjusting for ACO and beneficiary characteristics, however, ACOs serving the most deprived had a savings rate that was 2.3 percentage points lower than those serving the least deprived. CONCLUSIONS: ACOs serving deprived communities generate less savings. These findings are important to primary care practices, payers, and policy makers anticipating continued ACO expansion, if population health is to be achieved equitably.

Primary Care Physician Characteristics Associated with Low Value Care Spending.

BACKGROUND: Previous work has shown that $210 billion may be spent annually on unnecessary medical services and has identified patient and hospital characteristics associated with low value care (LVC). However, little is known about the association between primary care physician (PCP) characteristics and LVC spending. The objective of this study was to assess this association. METHODS: We performed a retrospective analysis by using Medicare claims data to identify LVC and American Medical Association Masterfile data for PCP characteristics. We included PCPs of adults aged 65 years and older who were enrolled in Medicare in 2011. We measured Medicare spending per attributed patient on 8 low value services. RESULTS: Our final sample contained 6,873 PCPs with 1,078,840 attributed patients. Lower per-patient LVC Medicare spending was associated with the following PCP characteristics: allopathic training, smaller Medicare patient panel, practiced family medicine, practiced in the Midwest region, were a recent graduate, or practiced in rural areas. The largest associations were seen in Medicare patient panel size and geographic region. The average per-patient LVC spending was $14.67. LVC spending among PCPs with small patient panels was $3.98 less per patient relative to those with larger panels. PCPs in the Midwest had $2.80 less per patient LVC spending than those in the Northeast. CONCLUSION: Our analysis suggests that LVC services are associated with specific PCP characteristics. Further research should assess the strength of these associations, and future policy efforts should focus on systemic interventions to reduce LVC spending.

Higher Primary Care Physician Continuity is Associated With Lower Costs and Hospitalizations.

PURPOSE: Continuity of care is a defining characteristic of primary care associated with lower costs and improved health equity and care quality. However, we lack provider-level measures of primary care continuity amenable to value-based payment, including the Medicare Quality Payment Program (QPP). We created 4 physician-level, claims-based continuity measures and tested their associations with health care expenditures and hospitalizations. METHODS: We used Medicare claims data for 1,448,952 beneficiaries obtaining care from a nationally representative sample of 6,551 primary care physicians to calculate continuity scores by 4 established methods. Patient-level continuity scores attributed to a single physician were averaged to create physician-level scores. We used beneficiary multilevel models, including beneficiary controls, physician characteristics, and practice rurality to estimate associations with total Medicare Part A & B expenditures (allowed charges, logged), and any hospitalization. RESULTS: Our continuity measures were highly correlated (correlation coefficients ranged from 0.86 to 0.99), with greater continuity associated with similar outcomes for each. Adjusted expenditures for beneficiaries cared for by physicians in the highest Bice-Boxerman continuity score quintile were 14.1% lower than for those in the lowest quintile ($8,092 vs $6,958; ß = -0.151; 95% CI, -0.186 to -0.116), and the odds of hospitalization were 16.1% lower between the highest and lowest continuity quintiles (OR = 0.839; 95% CI, 0.787 to 0.893). CONCLUSIONS: All 4 continuity scores tested were significantly associated with lower total expenditures and hospitalization rates. Such indices are potentially useful as QPP measures, and may also serve as proxy resource-use measures, given the strength of association with lower costs and utilization.

Physicochemical and Storage Characteristics of Hanwoo Tteokgalbi Treated with Onion Skin Powder and Blackcurrant Powder.

We evaluated the physicochemical and storage characteristics of Hanwoo Tteokgalbi treated with onion skin powder (OSP) and blackcurrant fruit powder (BFP). The experimental design included seven treatments: a control (ascorbic acid 0.1%), T1: OSP 0.3%, T2: OSP 0.6%, T3: BFP 0.3%, T4: BFP 0.6%, T5: OSP 0.15%+BFP 0.15%, and T6: OSP 0.3%+BFP 0.3%. The OSP was higher in both polyphenol and flavonoid contents compared to BFP (p<0.05). The moisture and ash contents of all Tteokgalbi samples with a large amount of added natural antioxidant powder (0.6%) were higher than those with small amounts of added antioxidant (0.3%). The cooking loss and water holding capacity were outstanding in the T2 treatment compared to the others (p<0.05). The lightness, redness, and yellowness values were reduced on the addition of 0.6% antioxidant powder (p<0.05). The springiness and cohesiveness values of the Tteokgalbi samples were higher for the 0.3% addition than the control and 0.6% addition (p<0.05). The Tteokgalbi samples with natural antioxidants showed similar sensory attribute scores compared to the control. The pH values reduced as the BFP increased (p<0.05), and the total microbial count increased after OSP addition. The 2-thiobarbituric acid reactive substance values of the samples treated with OSP were significantly lower than the control after day 10 (p<0.05). As a result, the addition of OSP or BFP did not have a significant negative influence on the quality characteristics of Hanwoo Tteokgalbi. In particular, the addition of 0.6% OSP was effective in increasing water retentivity and inhibiting lipid oxidation.

Effect of Rice Bran and Wheat Fibers on Microbiological and Physicochemical Properties of Fermented Sausages during Ripening and Storage.

This study investigated the effect of rice bran fiber (RBF) and wheat fibers (WF) on microbiological and physicochemical properties of fermented sausages during ripening and storage. The experimental design included three treatments: Control, no addition; RBF, 1.5%; and WF, 1.5%. During the ripening periods, the addition of dietary fibers rapidly decreased pH and maintained high water activity values of fermented sausages (p<0.05). Lactic acid bacteria were more prevalent in fermented sausages with rice bran fiber than control and sausages with added wheat fiber. During cold storage, lower pH was observed in sausages with dietary fibers (p<0.05), and the water activity and color values were reduced as the storage period lengthened. Fermented sausages containing dietary fibers were higher in lactic acid bacteria counts, volatile basic nitrogen and 2-thiobarbituric acid reactive substance values compared to the control (p<0.05). The results indicate that, the addition of dietary fibers in the fermented sausages promotes the growth of lactic bacteria and fermentation, and suggests that development of functional fermented sausages is possible.

A qualitative study exploring factors associated with Pap test use among North Korean refugees.

Lack of medical care in North Korea and vulnerability to human trafficking during their migration increase risks of cervical cancer among North Korean refugees. To better understand factors influencing Pap test use, we conducted a qualitative study of eight North Korean refugees in South Korea. Individual barriers were limited knowledge, lack of perceived need for preventive services, and concerns about costs. Environmental facilitators included having female providers, receiving family support, and free screenings. Refugees' health outlook, including viewing cancers as fatal diseases, hindered seeking Pap tests. Multi-faceted approaches to address individual and environmental factors in promoting Pap tests are warranted.

Medicaid use by documented and undocumented farm workers.

BACKGROUND: Despite considerable debate surrounding the use of Medicaid by undocumented immigrants, few studies address the extent of this use or estimate differences in the use between documented and undocumented households. METHOD: We analyzed data from the National Agricultural Workers Survey annual cross sections from 1993 through 2009, N = 41,342. Simple mean differences and logistic regressions predicted participation in Medicaid over 2-year intervals. RESULTS: Without adjustments for covariates, 12.2% of undocumented farm workers' households and 22.6% of documented households received Medicaid benefits, corresponding to an odds ratio of 0.48 (95% confidence interval, 0.33 to 0.69). By adding only covariates reflecting presence of children in the household, the odds ratio increased to 0.86 (95% confidence interval, 0.73 to 1.02). CONCLUSIONS: Undocumented farm workers' households were roughly half as likely to use Medicaid as documented households, and undocumented households' participation was especially responsive to the presence of children.

Characterization and application of enterocin RM6, a bacteriocin from Enterococcus faecalis.

Use of bacteriocins in food preservation has received great attention in recent years. The goal of this study is to characterize enterocin RM6 from Enterococcus faecalis OSY-RM6 and investigate its efficacy against Listeria monocytogenes in cottage cheese. Enterocin RM6 was purified from E. faecalis culture supernatant using ion exchange column, multiple C18-silica cartridges, followed by reverse-phase high-performance liquid chromatography. The molecular weight of enterocin RM6 is 7145.0823 as determined by mass spectrometry (MS). Tandem mass spectrometry (MS/MS) analysis revealed that enterocin RM6 is a 70-residue cyclic peptide with a head-to-tail linkage between methionine and tryptophan residues. The peptide sequence of enterocin RM6 was further confirmed by sequencing the structural gene of the peptide. Enterocin RM6 is active against Gram-positive bacteria, including L. monocytogenes, Bacillus cereus, and methicillin-resistant Staphylococcus aureus (MRSA). Enterocin RM6 (final concentration in cottage cheese, 80 AU/mL) caused a 4-log reduction in population of L. monocytogenes inoculated in cottage cheese within 30 min of treatment. Therefore, enterocin RM6 has potential applications as a potent antimicrobial peptide against foodborne pathogens in food.

Inactivation of barotolerant strains of Listeria monocytogenes and Escherichia coli O157:H7 by ultra high pressure and tert-butylhydroquinone combination.

Antimicrobial efficacy of ultra-high-pressure (UHP) can be enhanced by application of additional hurdles. The objective of this study was to systematically assess the enhancement in pressure lethality by TBHQ treatment, against barotolerant strains of Escherichia coli O157:H7 and Listeria monocytogenes. Two L. monocytogenes Scott A and the barotolerant OSY-328 strain, and two E. coli O157:H7 strains, EDL-933 and its barotolerant mutant, OSY-ASM, were tested. Cell suspensions containing TBHQ (50 ppm, dissolved in dimethyl sulfoxide) were pressurized at 200 to 500 MPa (23+/-2 degrees C) for 1 min, plated on tryptose agar and enumerated the survivors. The TBHQ-UHP combination resulted in synergistic inactivation of both pathogens, with different degrees of lethality among strains. The pressure lethality threshold, for the combination treatment, was lower for E. coli O157:H7 (> or = 200 MPa) than for L. monocytogenes (> 300 MPa). E. coli O157:H7 strains were extremely sensitive to the TBHQ-UHP treatment, compared to Listeria strains. Interestingly, a control treatment involving DMSO-UHP combination consistently resulted in higher inactivation than that achieved by UHP alone, against all strains tested. However, sensitization of the pathogens to UHP by the additives (TBHQ in DMSO) was prominently greater for UHP than DMSO. Differences in sensitivities to the treatment between these two pathogens may be attributed to discrepancies in cellular structure or physiological functions.

Genes of Escherichia coli O157:H7 that are involved in high-pressure resistance.

Seventeen Escherichia coli O157:H7 strains were treated with ultrahigh pressure at 500 MPa and 23 +/- 2 degrees C for 1 min. This treatment inactivated 0.6 to 3.4 log CFU/ml, depending on the strain. The diversity of these strains was confirmed by pulsed-field gel electrophoresis (PFGE) analysis, and there was no apparent association between PFGE banding patterns and pressure resistance. The pressure-resistant strain E. coli O157:H7 EC-88 (0.6-log decrease) and the pressure-sensitive strain ATCC 35150 (3.4-log decrease) were treated with a sublethal pressure (100 MPa for 15 min at 23 +/- 2 degrees C) and subjected to DNA microarray analysis using an E. coli K-12 antisense gene chip. High pressure affected the transcription of many genes involved in a variety of intracellular mechanisms of EC-88, including the stress response, the thiol-disulfide redox system, Fe-S cluster assembly, and spontaneous mutation. Twenty-four E. coli isogenic pairs with mutations in the genes regulated by the pressure treatment were treated with lethal pressures at 400 MPa and 23 +/- 2 degrees C for 5 min. The barotolerance of the mutants relative to that of the wild-type strains helped to explain the results obtained by DNA microarray analysis. This study is the first report to demonstrate that the expression of Fe-S cluster assembly proteins and the fumarate nitrate reductase regulator decreases the resistance to pressure, while sigma factor (RpoE), lipoprotein (NlpI), thioredoxin (TrxA), thioredoxin reductase (TrxB), a trehalose synthesis protein (OtsA), and a DNA-binding protein (Dps) promote barotolerance.