Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.

OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real-world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first-line tumor necrosis factor inhibitor (TNFi). METHODS: Data from adult patients with RA initiating a first-line TNFi were collected from the American Rheumatology Network (January 2014-August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. RESULTS: Among TNFi initiators (n = 15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n = 1,651), 52% discontinued their initial TNFi during follow-up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non-TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. CONCLUSION: In clinical practice, over half of patients with RA initiating a first-line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

Role of Apoptotic-targeted Phytoconstitutent-loaded Antipsoriatic Nanobiocomposites.

Psoriasis is an inflammatory and proliferative autoimmune dermatological disorder. It is a skin ailment that is defined by particular, drab-red or peach-pink stiff areas with silvery scales patches. Other typical characteristics include the proliferation of epidermal layer, aberrant keratinization, hyperkeratosis, increased micro capillary vascularization, and infiltration of inflammatory mediator loaded cells. Conventional pharmacotherapies currently available can only provide minor advantages. Nanomedicines based on nanotechnology can potentially improve the efficacy and safety of psoriasis medications. Apoptosis plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest, in particular, regarding psoriasis. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. We reviewed the available studies on the efficacy of antiapoptotic therapies in psoriasis. We'll look at phytochemicals in this review, which are natural components found in plants with antiapoptotic activity that are frequently used to treat psoriasis. For improved topical treatment, we also take into consideration the advantages of loading phytoconstituents as medicines into lipid based nanocarriers. The utilization of herbal nanomedicines in psoriasis, as well as nano delivery carrier system for phytoconstituents with improved therapeutic profiles and decreased toxicity, are the subjects of this review. The study's purpose is to find more effective herbal nanomedicines for treating psoriasis. In the treatment of psoriasis, phytoconstituents that have shown antipsoriatic potential in recent years, as well as phytoconstituents loaded based nanomedicines, have a lot of promising roles to be explored. Furthermore, very few patents have been found in the field of nanotechnology utilizing lipid-based nanocarrier system for the treatment of psoriasis. Therefore, this review greatly compels the researcher to validate the process development of lipid-based drug delivery system for the patentability of the product. This should be in a view of shifting in the applicability of the drug delivery system for general public health as a potential treatment option in psoriasis.

Demand and willingness to pay for human papilloma virus vaccine for their daughters among mothers in Haryana, India: A contingent valuation study.

OBJECTIVES: Cervical cancer accounts for 10 percent of cancer deaths among women in India. The human papillomavirus (HPV) vaccine can protect against infection but it is not included in India's universal immunisation programme. This study aimed to assess the demand and willingness to pay for the HPV vaccine among mothers of adolescent daughters. METHODS: We conducted a contingent valuation exercise involving a hospital-based cross-sectional study to assess the demand for an HPV vaccine among mothers of adolescent daughters, their willingness to pay and its determinants. Participants were recruited at a tertiary care civil hospital in the city of Gurgaon in North India, and data was collected from December 2018 to February 2019. A questionnaire was administered to obtain demographic and awareness indicators. Payment cards were used to elicit the willingness to pay amount. RESULTS: Out of 319 respondents, 79% were willing to pay for the vaccine. The mean maximum willingness to pay was INR 629 (USD 35), which was less than the vaccine market price of INR 2000-3000 (USD 117-175) per dose. Participant age and number of children significantly influenced demand, while family income and awareness of cervical cancer influenced willingness to pay for the HPV vaccine. Participants were willing to spend between 3% and 34% of their monthly income on the vaccine. CONCLUSIONS: High demand and low willingness to pay for the HPV vaccine indicate low value perception of the health outcome among mothers of adolescent children in India. A strategy aimed at a price reduction of the vaccine and increasing its demand through improved awareness is important. At the same time, subsidising the vaccine in the short run is needed.

Nonlinear effect of employee ownership on organizational financial misdeeds: The moderating role of organizational size.

We used threshold theory to investigate the relationship between employee ownership and financial misdeeds. In particular, we theorized that monitoring and incentive benefits of employee ownership coupled with longer term orientation are two primary theoretical drivers for decreasing the incidence of financial misdeeds in employee-owned firms. Using a sample of 388 investment firms representing 3,421 firm-year observations between 2000 and 2015, we found that employee ownership has an inverted-J-shaped relationship with organizational financial misdeeds such that the negative effect of employee ownership is significant only at medium-to-high levels. We also found that the inverted-J-shaped relationship was stronger when an organization was smaller or practiced giving short-term incentives. We discuss the theoretical and practical implications of these findings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Relative bed allocation for COVID-19 patients, EHR investments, and COVID-19 mortality outcomes.

Managing flexibility in the relative bed allocation for COVID-19 and non-COVID-19 patients was a key challenge for hospitals during the COVID-19 pandemic. Based on organizational information processing theory (OIPT), we propose that the local electronic health record (EHR) systems could improve patient outcomes through improved bed allocation in the local area. In an empirical analysis of county-level weekly hospital data in the US, relative capacity of beds in hospitals with higher EHR was associated with lower 7-, 14-, and 21-day forward-looking COVID-19 death rate at the county-level. Testing for cross-state variation in non-pharmaceutical interventions along contiguous county border-pair analysis to control for spatial correlation varying between state variations in non-pharmaceutical intervention policies, 2SLS analysis using quality ratings, and using foot-traffic data at the US hospitals our findings are generally supported. The findings have implications for policymakers and stakeholders of the local healthcare supply chains and EHR systems.

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

INTRODUCTION: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). METHODS: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. RESULTS: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. CONCLUSIONS: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

Molecular identification and genetic characterization of Theileria and Anaplasma infection in sheep and goat of North Gujarat, India.

Hemoprotozoal diseases are significant health concerns in small ruminants. The present study was conducted to identify and characterize the species of Theileria and Anaplasma in sheep and goats located in different districts of North Gujarat, India. A total of 226 (Banaskantha = 175, Patan = 26, and Bhuj = 25) blood samples were collected from sheep (n = 78) and goats (n = 148), and 46 ticks were collected and identified from sheep and goats. PCR assays were carried out using genus and species-specific primers for Theileria targeting 18S rRNA locus and for Anaplasma targeting the msp5 gene. Overall, 37.2% sheep (29/78) and 10.8% of goats (16/148) were positive for Theileria by PCR, whereas 15.4% of sheep (12/78) and 25.7% goats (38/148) were positive for Anaplasma infection. Moreover, mixed infection was found in 4.4% (10/226) of sheep and goats by PCR. Sanger sequencing of Theileria and Anaplasma positives revealed a high similarity to T. ovis and A. ovis using NCBI blast, respectively. Phylogenetic analyses revealed that the Anaplasma spp. DNA sequences belonged to the A. ovis group and closely associated with the A. ovis nucleotide sequence strain Haibei isolated in China from sheep (GQ483471). The phylogenetic analysis based on the SSU rRNA locus revealed that the Theileria ovis DNA sequences belonged to the T. ovis group and closely related to MW440586 isolated in Kerala, India, from a goat. The majority of ticks (91.3%) were identified as Hyalomma. In conclusion, Theileria ovis and Anaplasma ovis were commonly identified species in sheep and goats and transmitted mainly by Hyalomma ticks in North Gujarat, India, which is important baseline data for future research and control strategies. This is the first report on Theileria and Anaplasma co-infections in sheep and goats from North Gujarat, India.

Waste to energy: a decision-making process for technology selection through characterization of waste, considering energy and emission in the city of Ahmedabad, India.

Municipal solid waste (MSW) disposal has become major issue for the city of Ahmedabad, India. Development, concentrated population and economic growth have led to a substantial increase of MSW generation. Therefore, the objective of the study was to characterize MSW for selection of waste processing technology. To provide a solution for sustainable processing and for safe disposal of fresh MSW, Abellon Clean Energy Ltd joined forces with Ahmedabad Municipal Corporation (AMC) under Public-Private Partnership (PPP) to establish a 14.9MW advanced controlled combustion-based waste to energy (WTE) generation facility to process and dispose 1000 tons/day of fresh MSW. For waste characterization, samples (n=201) were collected from the Pirana waste dumping site using quadrate sampling method. A yearly weighted average Low Heating Value (LHV) of 9.85/kg and ash content 25.12% for unsegregated MSW makes controlled combustion with electricity generation an eligible technology. After combustion, the waste volume is reduced by 75%. The 14.9MW WTE facility replaces 417 t coal/day, reducing greenhouse gas (GHG) emissions of 300.38 tCO2eq/day through coal replacement, while avoiding 735.24 t CO2eq/day on account of landfill emissions from MSW dumping. Waste to energy is the fastest solution to reduce waste volume by generating electricity through reduction of GHG.

Continuity of Care Within a Single Patient Support Program for Patients with Rheumatoid Arthritis Prescribed Second or Later Line Advanced Therapy.

INTRODUCTION: Guidelines suggest patients with rheumatoid arthritis (RA) inadequately controlled by tumor-necrosis-factor-inhibitors (TNFis) may benefit from switching to Janus-kinase-inhibitors (JAKis); however, care coordination and access can be complicated. Disruptions in transitioning to JAKi treatment could lead to disease flares requiring hospitalization; however, transitioning between products within the same patient support program (PSP) services aimed at ensuring continuity of care may minimize disruptions. METHODS: A retrospective, longitudinal cohort study of adult patients with RA newly prescribed JAKi following TNFi treatment in the Symphony Health claims database. Patients with baseline TNFi use and ≥ 6 months of data before (baseline) and after (follow-up) the initial JAKi claim (approved or denied) were included. Cohorts were defined by transitions between products within the same PSP [adalimumab (ADA) and upadacitinib (UPA)] or not. Disruptions were defined as gap in care ≥ 15 days due to failure/delay in receiving coverage approval or picking up an approved prescription. Disruptions followed by JAKi dispense were considered temporary and those without permanent. Odds ratios (ORs) of disruption and hospitalization were estimated from logistic regressions controlling for patient characteristics and treatment history. RESULTS: A total of 2371 patients were included: 317 transitioning from ADA-UPA, 321 TNFi-UPA, 860 ADA-another JAKi, and 873 another TNFi-another JAKi. Temporary and permanent disruptions increased odds of hospitalization by 47% and 123% (both p < 0.05). Temporary disruption rates were lowest for ADA-UPA patients (19%) compared to other TNFi-UPA (25%; OR = 1.46), ADA-other JAKi (29%; OR = 1.59), and other TNFi-other JAKi (31%; OR = 1.74), all p < 0.05. For transitions to UPA, temporary disruptions were lower for patients using the PSP (17%) versus not (24%; OR = 1.45, p < 0.05). No differences were found for permanent disruptions. CONCLUSION: Disruptions for patients with RA transitioning from TNFi to JAKi treatment are associated with increased hospitalization rates. Transitioning between drugs within the same PSP could lower the risk of disruption.

Insight to Combat Post COVID-19 Mortality: Complications and their Biomarkers.

BACKGROUND: COVID-19 is a severe acute respiratory syndrome that has become a prominent source of morbidity and mortality around the world. With millions infected globally by the COVID-19 epidemic, long-term care for COVID-19 survivors has become a global concern. As a result, research into the long-term pulmonary and extrapulmonary consequences and complications of COVID is absolutely necessary. OBJECTIVES: In an attempt to better understand and mitigate post recovery mortality, early detection of the post recovery complication might prevent the severity of the complication and can be recovered. As per cases reported, post covid extrapulmonary complications were more than pulmonary complications. However, the post covid pulmonary complications were found to be more lethal and nonrecoverable in most of the cases than extrapulmonary complications. METHODS: The present review is an attempt to reveal the role and importance of biomarkers associated with critical post covid pulmonary complications. COVID-19 is associated with post-covid pulmonary fibrosis, pulmonary endothelial dysfunction, pulmonary aspergillosis, pulmonary mucormycosis, biomarkers and WHO, as keywords were used to retrieve updated information. PubMed, and Google Scholar were used as search engines for this. RESULTS: There must be a better knowledge of the post-COVID-19 pulmonary problems in terms of systemic pathophysiological results to create multidisciplinary clinics to address both long-term symptoms and potential long-term consequences. This can be achieved by revealing the molecular pathogenesis that can be validated by certain biomarkers and various diagnostic techniques. Accordingly, the clinical program can be designed to treat and effectively manage the post covid pulmonary complications in early-stage to prevent mortality. CONCLUSION: In order to deal with the specific logistical problems given by pandemic circumstances, effective interdisciplinary collaboration models draw on experiences learned during the early phases of the pandemic.

Right of association and new business entry: country-level evidence from the market sector.

Labor market institutions (LMIs) could enable new firm entry by lowering burdens to attracting and retaining human capital or restrict new firm entry by increasing concerns of additional demands on ventures facing liabilities of newness and smallness. In this study, we focus on the LMI of the right of association, and whether its relationship with new business entry depends on the vertical ordering of bargaining (represented in the centralization of collective bargaining) or the horizontal synchronization of wage-setting (represented in the coordination of wage-setting). In a panel of 44 countries covering the period 2005-2019, we find that the right of association in the market sector is positively associated with new business entry; however, with increasing centralization of collective bargaining, the association becomes negative. Coordination of wage-setting does not significantly affect the relationship between the right of association and new business entry. The results are robust to accounting for both serial correlation and cross-sectional correlation in the panel regressions and carry implications for policymakers regarding the effects of LMIs on new business creation.

A comparison of marginal bone loss, survival rate, and prosthetic complications in implant-supported splinted and nonsplinted restorations: A systematic review and meta-analysis.

Aim: To compare marginal bone loss (MBL), implant survival rate and prosthetic complications of implant-supported splinted and non-splinted restorations (NSR). Settings and Design: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA). The PROSPERO registry, which keeps track of prospective systematic reviews, also received this paper (CRD42021229477). Material and Methods: An electronic search was done in PubMed, the Cochrane Central Trials Register, Scopus, Science Direct, and Google Scholar searches were carried out. The search was limited to articles published in English and covered the period from January 2010 to August 2020. Statistical Analysis Used: To conduct the meta analysis, researchers employed methodologies such as continuous measurement and odds ratios. Results: For both qualitative and quantitative analysis, 19 scientific studies were chosen. 3682 implants were placed in 2099 patients with a mean age of 59 years (splinted, 2529; non-splinted, 1153); the mean age was not provided in 5 trials. For splinted restorations, there were statistically significant differences in MBL, indicating the former has less MBL than for NSR. Splinted restorations had much greater survival rates than NSR, according to a qualitative study. Rest prosthesis complications with or without splinting were essentially the same. Conclusions: Splinted implant restorations lost less bone than non-splinted implant restorations, according to this meta analysis. This was particularly true for posterior restorations. Lower implant failure was associated with splinted restorations. Restorations with and without splinting had the same level of prosthetic problems.

Whole genome sequencing and characteristics of extended-spectrum beta-lactamase producing Escherichia coli isolated from poultry farms in Banaskantha, India.

Worldwide dissemination of extended-spectrum -lactamase (ESBL)-producing Escherichia coli constitutes an emerging global health issue, with animal food products contributing as potential reservoirs. ESBL E. coli infection is associated with the high mortality and mobility rate in developing countries due to less susceptibility to antibiotics. The present study aimed to elucidate the molecular characteristics and sequence-based analysis of ESBL E. coli in the Gujarat state of India. This study included 108 E. coli strains were isolated from different poultry farms (broiler and layer) in the Banaskantha District. PCR was employed to identify genotypic ESBL-producing antimicrobial resistance genes. Overall, a high occurrence of ESBL genes was found in poultry farms due to the high usage of antimicrobials. The PCR analysis revealed that 79.62% of isolates were detected positive with one or more ESBL genes. Among them, bla TEM (63.88%) was found to be the predominant genotype, followed by bla SHV (30.55%) and bla OXA (28.70%). In the bla CTX-M group, a higher occurrence was observed in bla CTX-M-9 (23.14%), followed by bla CTX-M-2 (24.07%) and bla CTX-M-1 (22.22%). We used the whole-genome sequencing (WGS) method to evaluate the antimicrobial resistance genes, virulence factors, single nucleotide polymorphisms (SNPs), plasmid replicons, and plasmid-mediated AMR genes of one ESBL E. coli isolated. We examined the genetic relatedness of a human pathogenic E. coli strain by comparing its sequence with the broad geographical reference E. coli sequences. Escherichia coli ST 681 was determined using multi-locus sequence typing. We compared our findings to the reference sequence of Escherichia coli str. K- 12 substr. MG1655. We found 24,937 SNPs with 21,792 in the genic region, 3,145 in the intergenic region, and six InDels across the genome. The WGS analysis revealed 46 antimicrobial resistance genes and seven plasmid-mediated AMR genes viz., tetA, qnrS1, dfrA14, sul2, aph(3")-lb, aph(6)-ld, and Aph(3')-la. The ST 681 was found to have Cib, traT, and terC virulence factors and two plasmid replicons, IncFII(pHN7A8) and IncI1-I(Alpha). This study revealed a higher occurrence of ESBL E. coli detected in poultry.

Estimated size of the clinical medical imaging physics workforce in the United States.

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United States in 2019 consisted of approximately 1794 physicists supporting diagnostic X-ray (1073 board-certified) and 934 physicists supporting nuclear medicine (460 board-certified), with a number of individuals practicing in both subfields. There were an estimated 235 physicists supporting nuclear medicine exclusively (150 board-certified). The estimated total workforce, accounting for overlap, was 2029 medical physicists. These estimates are in approximate agreement with other published studies of segments of the workforce.

Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).

Impact of the COVID-19 pandemic on the hours lost by self-employed racial minorities: evidence from Brazil.

Drawing on minority enclave theory and resilience theory in entrepreneurship, we test whether, with the onset of the COVID-19 pandemic, the self-employed lost more hours than the employed and whether traditionally disadvantaged self-employed racial minorities faced harsher penalties in the form of reduced hours of work. Though spatially concentrated ethnic minority colocations could improve business outcomes in the non-crisis period, with the pandemic affecting all the members in the enclave, the very dependencies in minority enclaves could be a liability. Using a large-scale survey during the COVID-19 pandemic conducted by the Brazilian government, we draw on a one-to-one nearest neighbor matched pair sample of 19,626 employed (public or private sector) and self-employed individuals, and control for industry-sector-interview-location fixed effects. The results show that self-employed people, compared to employed, reported a greater loss of hours. At the sample level, black self-employed people on aggregate lost 9,051 hours per month, and mixed race self-employed people on aggregate lost 27,880 hours per month. The disproportionate loss of work hours by the self-employed from racial minority groups during the COVID-19 pandemic in a developing country context calls for a closer examination and assessment of the long-term impact of COVID-19 on racial minorities.

Estimation of ZYKR1 in human urine and plasma utilizing LC-MS/MS positive electrospray ionization; a kappa opioid receptor (KOR) agonist.

ZYKR1, a short chain novel peptide with selective kappa opioid receptor agonist activity used as analgesics for the treatment of pain management. A sensitive and selective LC-MS/MS assay was developed and validated for estimation of ZYKR1 in human urine and plasma. ZY17258, an analogue compound was used as an internal standard. ZYKR1 was quantified using a selective reaction monitoring in electrospray ionization positive mode. The chromatographic separation was performed using mobile phase consisted of 0.05% v/v formic acid in water and methanol in gradient elution by analytical column Kinetex C8, 100 A°, 5 µm, 100 × 4.6 mm with 8.0 min analytical run time. Solid Phase extraction technique was used for purification of ZYKR1 and IS from human urine and plasma. The calibration curves were linear over range of 0.300 ng/mL to 300 ng/mL and 0.500 ng/mL to 500 ng/mL for human urine and plasma, respectively. No matrix effect and no significant carryover were observed. The extraction recovery was consistent and ranged from about 85% to 93% in human urine and in plasma respectively. Inter-day and intra-day accuracy (bias, %) and precision (CV, %) was -11.11 to 5.91 % and -2.25 to 6.65 % in human urine and -2.74 to 7.17 % and 2.24 to 15.18 % in plasma respectively were well within the acceptance criteria. Both the assays were devoid of endogenous matrix interference and commonly used concomitant drug interference. The validated assays were used for estimation of ZYKR1 from clinical pharmacokinetic study sample bioanalysis in healthy human subjects.

Corticosteroids Do Not Increase the Likelihood of Primary Clostridioides difficile Infection in the Setting of Broad-Spectrum Antibiotic Use.

BACKGROUND: The pathogenesis of Clostridioides difficile infection (CDI) involves a significant host immune response. Generally, corticosteroids act by suppressing the host inflammatory response, and their anti-inflammatory effects are used to treat gastrointestinal disorders. Although previous investigations have demonstrated mixed results regarding the effect of corticosteroids on CDI, we hypothesized that the anti-inflammatory effect of corticosteroids would decrease the risk of CDI in hospitalized patients. METHODS: This was a case-control study of hospitalized adults. The case population included patients diagnosed with primary CDI who received at least 1 dose of a high-risk antibiotic (cefepime, meropenem, or piperacillin-tazobactam) in the 90 days before CDI diagnosis. The control population included patients who received at least 1 dose of the same high-risk antibiotic but did not develop CDI in the 90 days following their first dose of antibiotic. The primary study outcome was the development of CDI based on receipt of corticosteroids. RESULTS: The final study cohort consisted of 104 cases and 153 controls. Those who received corticosteroids had a lower odds of CDI after adjusting for age, proton pump inhibitor use, and antibiotic days of therapy (odds ratio, 0.54; 95% CI, 0.30-0.97; P = .04). We did not observe an association between corticosteroid dose or duration and CDI. CONCLUSIONS: We demonstrated a 46% relative reduction in the odds of developing CDI in patients who received corticosteroids in the past 90 days. We believe that our results provide the best clinical evidence to further support mechanistic studies underlying this phenomenon.

Mannose-binding lectin-associated serine protease-1 cleaves plasminogen and plasma fibronectin: prefers plasminogen over known fibrinogen substrate.

Mannose-binding lectin-associated serine protease-1 (MASP-1) is known to interact with complement and coagulation pathways. Recently it was reported that MASP-1 interacts with the fibrinolytic system but details remain unclear. The objective of the study is to find MASP-1 substrates that participate in the fibrinolytic system. Commercially available fibrinogen might contain some impurities. Fibrinogen was treated with MASP-1 followed by analysis on SDS-PAGE and the obtained cleaved fragments were identified by matrix-assisted laser desorption/ionization-time of flight/time of flight. Functional analysis of identified substrate was confirmed by fluorogenic and turbidimetric assay. Statistical analysis was done by using the Student t test. This study reports that plasminogen and plasma fibronectin are two hitherto unknown substrates of MASP-1. Conversion of plasminogen to plasmin like molecule by MASP-1 was confirmed by cleavage of plasmin specific substrate and digestion of fibrin clot. The role of MASP-1 in clot dissolution was confirmed by turbidity assay. Our study shows that MASP-1 selects plasminogen over fibrinogen to be a preferable substrate. MASP-1 promotes the fibrinolytic activity by the generation of plasmin like molecule from plasminogen and further destabilizes the clot by digestion of plasma fibronectin.