Beneficial effect of temporary methotrexate interruption on B and T cell responses upon SARS-CoV-2 vaccination in patients with rheumatoid arthritis or psoriatic arthritis.

B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.

Malposition of a Femoral Tunneled Dialysis Catheter through a Patent Foramen Ovale.

Patent foramen ovale (PFO) is a common congenital abnormality of high prevalence in adults. Its clinical significance is magnified in a right-to-left shunt, where paradoxical embolism can have catastrophic outcomes involving the brain, heart, mesenteric circulation, or extremities. Right-to-left shunting through a PFO is caused by increased right atrial pressure, as seen in the setting of pulmonary artery hypertension or pulmonary embolism. This case highlights the relevance of central venous catheter placement in the setting of a PFO. While the patient did not experience clinical sequelae from line placement, she was at high risk for paradoxical embolus. Recognizing the possibility of a PFO during central venous catheter placement, especially in the setting of increased right pressures, should be a consideration of all interventional radiologists.

Cm-p5 Peptide Dimers Inhibit Biofilms of Candida albicans Clinical Isolates, C. parapsilosis and Fluconazole-Resistant Mutants of C. auris.

Antimicrobial peptides (AMPs) represent a promising class of therapeutic biomolecules that show antimicrobial activity against a broad range of microorganisms, including life-threatening pathogens. In contrast to classic AMPs with membrane-disrupting activities, new peptides with a specific anti-biofilm effect are gaining in importance since biofilms could be the most important way of life, especially for pathogens, as the interaction with host tissues is crucial for the full development of their virulence in the event of infection. Therefore, in a previous study, two synthetic dimeric derivatives (parallel Dimer 1 and antiparallel Dimer 2) of the AMP Cm-p5 showed specific inhibition of the formation of Candida auris biofilms. Here we show that these derivatives are also dose-dependently effective against de novo biofilms that are formed by the widespread pathogenic yeasts C. albicans and C. parapsilosis. Moreover, the activity of the peptides was demonstrated even against two fluconazole-resistant strains of C. auris.

Antimicrobial Peptides: Avant-Garde Antifungal Agents to Fight against Medically Important Candida Species.

Expanding the antifungal drug arsenal for treating Candida infections is crucial in this era of the rising life expectancy of patients with immunosuppression and comorbidities. Infections caused by Candida species are on the rise, including those caused by multidrug-resistant strains or species, and the list of antifungals approved for the treatment of these infections is still limited. Antimicrobial peptides (AMPs) are short cationic polypeptides whose antimicrobial activity is under intense investigation. In this review, we present a comprehensive summary of the AMPs with anti-Candida activity that have undergone successful preclinical or clinical trials. Their source, mode of action, and animal model of infection (or clinical trial) are presented. In addition, as some of these AMPs have been tested in combination therapy, the advantages of this approach, as well as the studied cases that have used AMPs and other drugs concomitantly to fight Candida infections, are described.

Toward the Identification of Distinct Phenotypes: Research Protocol for the Low Back Pain Biological, Biomechanical, and Behavioral (LB3P) Cohort Study and the BACPAC Mechanistic Research Center at the University of Pittsburgh.

As a member of the Back Pain Consortium (BACPAC), the University of Pittsburgh Mechanistic Research Center's research goal is to phenotype chronic low back pain using biological, biomechanical, and behavioral domains using a prospective, observational cohort study. Data will be collected from 1,000 participants with chronic low back pain according to BACPAC-wide harmonized and study-specific protocols. Participation lasts 12 months with one required in person baseline visit, an optional second in person visit for advanced biomechanical assessment, and electronic follow ups at months 1, 2, 3, 4, 5, 6, 9, and 12 to assess low back pain status and response to prescribed treatments. Behavioral data analysis includes a battery of patient-reported outcomes, social determinants of health, quantitative sensory testing, and physical activity. Biological data analysis includes omics generated from blood, saliva, and spine tissue. Biomechanical data analysis includes a physical examination, lumbopelvic kinematics, and intervertebral kinematics. The statistical analysis includes traditional unsupervised machine learning approaches to categorize participants into groups and determine the variables that differentiate patients. Additional analysis includes the creation of a series of decision rules based on baseline measures and treatment pathways as inputs to predict clinical outcomes. The characteristics identified will contribute to future studies to assist clinicians in designing a personalized, optimal treatment approach for each patient.

Ehlers-Danlos: A Literature Review and Case Report in a Colombian Woman with Multiple Comorbidities.

Ehlers-Danlos syndromes (EDS) are a heterogeneous group of genetically transmitted connective tissue disorders that directly affect collagen synthesis, with a broad range of symptoms. Case presentation: This study presents a clinical case of a Colombian woman with myopathic EDS and multiple comorbidities taking 40 years of medical history to make the right diagnosis. This article also presents a review of the current literature on EDS, not only to remind the syndrome but also to help the clinician correctly identify symptoms of this diverse syndrome. Conclusion: A multidisciplinary approach to the diagnosis of the patient, including clinical and molecular analysis, and neuropsychological and psychological assessment, is important to improve the treatment choice and the outcome prediction of the patients.

Factors Associated With Burnout in Physical Medicine and Rehabilitation Residents in the United States.

OBJECTIVES: The aims of the study were to determine the prevalence of burnout in physical medicine and rehabilitation residents in the United States and to identify the personal- and program-specific characteristics most strongly associated with residents reporting burnout. DESIGN: This was a cross-sectional survey of US physical medicine and rehabilitation residents. Emotional exhaustion, depersonalization, and burnout were assessed using two validated items from the Maslach Burnout Inventory. Associations of burnout with demographics and personal factors, residency program characteristics, perceived program support, and work/life balance were evaluated. RESULTS: The survey was completed by 296 residents (22.8%), with 35.8% of residents meeting the criteria for burnout. Residents' perception of not having adequate time for personal/family life was the factor most strongly associated with burnout (χ2 = 93.769, P < 0.001). Residents who reported inappropriate clerical burden and working more than 50 hrs/wk on inpatient rotations were most likely to report that they did not have adequate time for personal/family life. Faculty support (χ2 = 41.599, P < 0.001) and performing activities that led residents to choose physical medicine and rehabilitation as a specialty (χ2 = 93.082, P < 0.001) were protective against burnout. CONCLUSIONS: Residents reporting having inadequate time for their personal/family life was most strongly associated with physical medicine and rehabilitation resident burnout, although many personal and program characteristics were associated with burnout.

It Takes a Village: Expanding Women's Cardiovascular Care to Include the Community as well as Cardiovascular and Primary Care Teams.

PURPOSE OF REVIEW: Our aim is to highlight some of the current issues that prevent women from getting sex-specific and gender-specific cardiovascular care and provide recommendations for new approaches and delivery models to improve cardiovascular care for all women. RECENT FINDINGS: Cardiovascular disease remains the number one cause of death for women in the US. Many women remain unaware of cardiovascular risk factors and many healthcare providers who care for women are also poorly informed and feel ill prepared to assess women for cardiovascular risk. Women's Heart Centers have tried to bridge the gaps in women's care between primary care and cardiology. Many of the impediments to care in the current models are lack of comprehensive care and socioeconomic societal limitations. New models of care and delivery are essential to change cardiovascular outcomes for all women, especially women at high risk.

Predictors of posttraumatic stress symptom severity and meaning made in treatment-seeking veterans.

OBJECTIVE: Combat-exposed veterans risk encountering events that disrupt beliefs. To facilitate reduced discrepancy between prior beliefs and current trauma appraisals, veterans may engage in a process of meaning-making. Meaning-making can lead to positive outcomes, such as integrating the traumatic event into one's life narrative or adapting global meaning (meaning made) or elicit distress. Given these potentially different outcomes, this study examined potential correlates of posttraumatic stress symptom (PTSS) severity and meaning made, including relationship attachment dimensions of anxiety and avoidance, and difficulties with emotion regulation, while controlling for combat exposure. METHOD: Veterans receiving mental health services at a Veterans Affairs (VA) Medical Center and a VA community-based outpatient clinic (N = 130) completed measures through a paper-and-pencil survey. Almost all participants (92%) were male, with a mean age of 55.92 years. RESULTS: In terms of meaning made, lower levels of attachment anxiety and emotional clarity (an aspect of emotion regulation) predicted higher meaning made. In terms of PTSS severity, higher attachment avoidance, attachment anxiety, and difficulties engaging in goal-directed behavior (an aspect of emotion regulation) significantly predicted higher PTSS severity. CONCLUSION: Aspects of both attachment style and emotion regulation difficulties affect meaning made and PTSS severity. These constructs may be especially relevant for clinicians working with veterans to help PTSS and support meaning made postcombat.

Socioeconomic characteristics of African American women attending community blood pressure screenings.

Study objective: To examine the associations of education and income and blood pressure (BP) in a socioeconomically diverse cohort of African-American (AA) women attending community BP screenings. Design setting and participants: This cross-sectional analysis used data from AA women (n = 972) 53 ± 14 years, enrolled between 2015 and 2019 in the 10,000-women hypertension community screening project in the metropolitan Atlanta area. OLS linear regression were used to examine the associations between SES (education and income) and BP after adjusting for age, body mass index (BMI), smoking, and lipids. Main outcomes and measures: Outcomes were systolic and diastolic BP (SBP, DBP). Measures of SES included education [high school ≤(HS), some college, and ≥college] and income-[<$24,000, $24,000-<$48,000, $48,000-$96,000, and ≥$96,000]. Sociodemographics, health history, anthropometrics and point of care non-fasting lipids were obtained. Results: Compared to women earning <$24,000, an income of ≥$96,000 (ß = -5.7 mmHg, 95% CI: -9.9, -1.5, p = .01) was associated with a lower SBP in the minimally adjusted model. Subsequent adjustment for cardiovascular risk factors attenuated the association and was no longer significant. College and above versus ≤HS education was associated with a higher DBP in the minimally (ß = 2.7 mmHg, 95% CI: 0.2, 5.2, p = .03) and fully adjusted models (ß = 3.4 mmHg, 95% CI: 0.2, 6.5, p = .04). Conclusion: Income of ≥$96,000 was associated with a lower SBP while a college and above education was associated with a higher DBP. Findings underscore the need for increased cardiovascular risk awareness and education targeting higher SES AA women attending community BP screenings.

In-Hospital Complications in Pregnancies Conceived by Assisted Reproductive Technology.

Background Assisted reproductive technology (ART) has emerged as a common treatment option for infertility, a problem that affects an estimated 48 million couples worldwide. Advancing maternal age with increasing prepregnancy cardiovascular risk factors, such as chronic hypertension, obesity, and diabetes, has raised concerns about pregnancy complications associated with ART. However, in-hospital complications following pregnancies conceived by ART are poorly described. Methods and Results To assess the patient characteristics, obstetric outcomes, vascular complications and temporal trends of pregnancies conceived by ART, we analyzed hospital deliveries conceived with or without ART between January 1, 2008, and December 31, 2016, from the United States National Inpatient Sample database. We included 106 248 deliveries conceived with ART and 34 167 246 deliveries conceived without ART. Women who conceived with ART were older (35 versus 28 years; P<0.0001) and had more comorbidities. ART-conceived pregnancies were independently associated with vascular complications (acute kidney injury: adjusted odds ratio [aOR], 2.52; 95% CI 1.99-3.19; and arrhythmia: aOR, 1.65; 95% CI, 1.46-1.86), and adverse obstetric outcomes (placental abruption: aOR, 1.57; 95% CI, 1.41-1.74; cesarean delivery: aOR, 1.38; 95% CI, 1.33-1.43; and preterm birth: aOR, 1.26; 95% CI, 1.20-1.32), including in subgroups without cardiovascular disease risk factors or without multifetal pregnancies. Higher hospital charges ($18 705 versus $11 983; P<0.0001) were incurred compared with women who conceived without ART. Conclusions Pregnancies conceived by ART have higher risks of adverse obstetric outcomes and vascular complications compared with spontaneous conception. Clinicians should have detailed discussions on the associated complications of ART in women during prepregnancy counseling.

The Mental and Physical Health of Mothers of Children with Special Health Care Needs in the United States.

OBJECTIVE: To determine the prevalence of poor mental and physical health among mothers of children with special health care needs (CSHCN) and to determine the association between maternal health and the child's number of special health care needs (SHCN) and severity of ability limitation. METHODS: We used the combined 2016-2018 National Survey of Children's Health Dataset of 102,341 children ages 0-17 including 23,280 CSHCN. We used regression models to examine the associations of a child's number of SHCN and ability limitations with maternal health. RESULTS: Twice as many mothers of CSHCN had poor mental and physical health compared to non-CSHCN (mental 10.3% vs. 4.0%, p < .001; physical 11.9% vs 5.0%, p < .001). In regression models, increased number of SHCN and severity of activity limitations were associated with significantly increased odds of poor maternal health. CONCLUSIONS FOR PRACTICE: Mothers of CSHCN have worse health compared to mothers of non-CSHCN, especially those who experience social disadvantage and those with children with complex SHCN or severe ability limitations. Interventions to improve the health of these particularly vulnerable caregivers of CSHCN are warranted.

A roadmap to reduce information inequities in disability with digital health and natural language processing.

People with disabilities disproportionately experience negative health outcomes. Purposeful analysis of information on all aspects of the experience of disability across individuals and populations can guide interventions to reduce health inequities in care and outcomes. Such an analysis requires more holistic information on individual function, precursors and predictors, and environmental and personal factors than is systematically collected in current practice. We identify 3 key information barriers to more equitable information: (1) a lack of information on contextual factors that affect a person's experience of function; (2) underemphasis of the patient's voice, perspective, and goals in the electronic health record; and (3) a lack of standardized locations in the electronic health record to record observations of function and context. Through analysis of rehabilitation data, we have identified ways to mitigate these barriers through the development of digital health technologies to better capture and analyze information about the experience of function. We propose 3 directions for future research on using digital health technologies, particularly natural language processing (NLP), to facilitate capturing a more holistic picture of a patient's unique experience: (1) analyzing existing information on function in free text documentation; (2) developing new NLP-driven methods to collect information on contextual factors; and (3) collecting and analyzing patient-reported descriptions of personal perceptions and goals. Multidisciplinary collaboration between rehabilitation experts and data scientists to advance these research directions will yield practical technologies to help reduce inequities and improve care for all populations.

Understanding help-seeking in rural counties: A serial mediation analysis.

OBJECTIVE: Rural areas in the Southern United States are characterized by certain cultural values that may delay or prevent mental health service utilization. The present study examined a four-stage chain of serial mediation where higher levels of general self-reliance would be related to greater levels of public stigma, which would in turn be related to higher levels of self-stigma, followed by greater self-reliance about managing mental health problems, and finally, more negative attitudes toward seeking help from psychologists. METHOD: Community members who lived in rural counties in the Southern United States (N = 783) completed measures of these constructs online. RESULTS: Mediation analyses supported a direct association between general self-reliance and attitudes toward help-seeking that was explained in serial by higher levels of public stigma, self-stigma, and mental health self-reliance. CONCLUSIONS: Clinical implications for rural practitioners are suggested including instilling policy changes, increasing provider visibility, and addressing barriers in therapy.

Automated Audiometry in Quiet and Simulated Exam Room Noise for Listeners with Normal Hearing and Impaired Hearing.

BACKGROUND: Up to 80% of audiograms could be automated which would allow more time for provision of specialty services. Ideally, automated audiometers would provide accurate results for listeners with impaired hearing as well as normal hearing. Additionally, accurate results should be provided both in controlled environments like a sound-attenuating room but also in test environments that may support greater application when sound-attenuating rooms are unavailable. Otokiosk is an iOS-based system that has been available for clinical use, but there are not yet any published validation studies using this product. PURPOSE: The purpose of this project was to complete a validation study on the OtoKiosk automated audiometry system in quiet and in low-level noise, for listeners with normal hearing and for listeners with impaired hearing. RESEARCH DESIGN: Pure tone air conduction thresholds were obtained for each participant for three randomized conditions: standard audiometry, automated testing in quiet, and automated testing in noise. Noise, when present, was 35 dBA overall and was designed to emulate an empty medical exam room. STUDY SAMPLE: Participants consisted of 11 adults with hearing loss and 15 adults with normal hearing recruited from the local area. DATA COLLECTION AND ANALYSIS: Thresholds were measured at 500, 1,000, 2,000, and 4,000 Hz using the Otokiosk system that incorporates a modified Hughson-Westlake method. Results were analyzed using descriptive statistics and also by a linear mixed-effects model to compare thresholds obtained in each condition. RESULTS: Across condition and participant group 73.6% of thresholds measured with OtoKiosk were within ± 5 dB of the conventionally measured thresholds; 92.8% were within ± 10 dB. On average, differences between tests were small. Pairwise comparisons revealed thresholds were ∼3.5-4 dB better with conventional audiometry than with the mobile application in quiet and in noise. Noise did not affect thresholds measured with OtoKiosk. CONCLUSIONS: The OtoKiosk automated hearing test measured pure tone air conduction thresholds from 500 to 4,000 Hz at slightly higher thresholds than conventional audiometry, but less than the smallest typical 5 dB clinical step-size. Our results suggest OtoKiosk is a reasonable solution for sound booths and exam rooms with low-level background noise.

Perturbation of cortical activity elicits regional and age-dependent effects on unconstrained reaching behavior: a pilot study.

Contributions from premotor and supplementary motor areas to reaching behavior in aging humans are not well understood. The objective of these experiments was to examine effects of perturbations to specific cortical areas on the control of unconstrained reaches against gravity by younger and older adults. Double-pulse transcranial magnetic stimulation (TMS) was applied to scalp locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Stimulation was intended to perturb ongoing activity in the targeted cortical region before or after a visual cue to initiate moderately paced reaches to one of three vertical target locations. Regional effects were observed in movement amplitude both early and late in the reach. Perturbation of PMA increased reach distance before the time of peak velocity to a greater extent than all other regions. Reaches showed greater deviation from a straight-line path around the time of peak velocity and greater overall curvature with perturbation of PMA and M1 relative to SMA and DLPFC. The perturbation increased positional variability of the reach path at the time of peak velocity and the time elapsing after peak velocity. Although perturbations had stronger effects on reaches by younger subjects, this group exhibited less reach path variability at the time of peak velocity and required less time to adjust the movement trajectory thereafter. These findings support the role of PMA in visually guided reaching and suggest an age-related change in sensorimotor processing, possibly due to a loss of cortical inhibitory control.

In-Hospital Complications in Pregnant Women With Current or Historical Cancer Diagnoses.

OBJECTIVE: To assess the temporal trends, characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery. METHODS: We analyzed delivery hospitalizations with or without current or historical cancer between January 1, 2004, and December 31, 2014, from the US National Inpatient Sample database. RESULTS: We included 43,132,097 delivery hospitalizations with no cancer, 39,118 with current cancer, and 67,336 with historical diagnosis of cancer. The 5 most common types of current cancer were hematologic, thyroid, cervical, skin, and breast cancer. Women with current and historical cancer were older (29 years and 32 years vs 27 years) and incurred higher hospital costs ($4131 and $4078 vs $3521) compared with women without cancer. Most of the cancer types were associated with preterm birth (hematologic: adjusted odds ratio [aOR], 1.48 [95% CI, 1.35 to 1.62]; cervical: aOR, 1.47 [95% CI, 1.32 to 1.63]; breast: aOR, 1.93 [95% CI, 1.72 to 2.16]). Current hematologic cancer was associated with the highest risk of peripartum cardiomyopathy (aOR, 12.19 [95% CI, 7.75 to 19.19]), all-cause mortality (aOR, 6.50 [95% CI, 2.22 to 19.07]), arrhythmia (aOR, 3.82 [95% CI, 2.04 to 7.15]), and postpartum hemorrhage (aOR, 1.31 [95% CI, 1.11 to 1.54]). Having a current or historical cancer diagnosis did not confer additional risk for stillbirth; however, metastases increased the risk of maternal mortality and preterm birth. CONCLUSION: Women with a current or historical diagnosis of cancer at delivery have more comorbidities compared with women without cancer. Clinicians should communicate the risks of multisystem complications to these complex patients.