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.
ABSTRACT
Introduction
Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study ...we examine the impact of hATTR amyloidosis on quality of life (QOL).
Methods
Neuropathy‐specific QOL, measured with the Norfolk QOL‐Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36‐item Short Form Health Survey version 2 (SF‐36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases.
Results
Neuropathy‐specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure.
Discussion
Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169–175, 2019
Abstract Background To compare outcomes for individuals with major depressive disorder (MDD) with or without subthreshold hypomania (mixed features) in naturalistic settings. Methods Using the Optum ...Research Database (1/1/2009─10/31/2014), a retrospective analysis of individuals newly diagnosed with MDD was conducted. Continuous enrollment for 12-months before and after the initial MDD diagnosis was required. MDD with subthreshold hypomania (mixed features) (MDD-MF) was defined based on ≥1 hypomania diagnosis within 30 days after an MDD diagnosis during the one-year follow-up period, in the absence of bipolar I diagnoses. Psychiatric medication use, healthcare utilization, and costs during the one-year follow-up period were compared using multivariate logistic and gamma regressions, controlling for baseline differences. Results Of 130,626 MDD individuals, 652 (0.5%) met the operational definition of MDD-MF. Compared to the MDD-only group, the MDD-MF group had more suicidality (2.0% vs. 0.5%), anxiety disorders (46.8% vs. 34.0%), and substance use disorders (15.5% vs. 6.1%, all P<0.001). More individuals with MDD-MF were treated with antidepressants (83.6% vs. 71.6%), mood stabilizers (50.5% vs. 2.7%), atypical antipsychotics (39.0% vs. 5.5%), and polypharmacy with multiple drug classes (72.1% vs. 22.7%, all P<0.001). Individuals with MDD-MF had higher hospitalizations rates (24.2% vs. 10.5%) and total healthcare costs (mean: $15,660 vs. $10,744, all P<0.001). Limitations The commercial claims data used were not collected for research purposes and may over- or under-represent certain populations. No specific claims-based diagnostic code for MDD with mixed features exists. Conclusions Greater use of mood stabilizers, atypical antipsychotics, polypharmacy, and healthcare resources provides evidence of the complexity and severity of MDD-MF. Identifying optimal treatment regimens for this population represents a major unmet medical need.
We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly.
Data were extracted from the Integrated Healthcare Information ...Services claims database (1999-2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode.
Elderly patients with gout (n = 2237) with high (6-8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7-2.6; OR 3.4, 95% CI 2.6-4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001).
Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.
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.
Introduction
The impact of the COVID-19 pandemic on routine medical care may result in altered healthcare resource use in patients with immune-mediated conditions. The aim of this study was to ...determine the impact of treatment interruptions in patients with and without COVID-19 infections who were treated with targeted immunomodulators (TIMs) in the USA.
Methods
Data from the IBM
®
MarketScan
®
Research Databases were analyzed in patients with immune-mediated conditions from January 1, 2018, through December 31, 2020. Healthcare resource use (HCRU) including hospitalizations, emergency department (ED) visits, in-person outpatient visits, and respiratory outcomes was assessed in a cohort of patients without COVID-19 who had uninterrupted versus interrupted TIM use. The impact of treatment interruption on HCRU and respiratory outcomes was also evaluated in a cohort of patients with COVID-19. Results from adjusted logistic regression were reported as adjusted odds ratios (aORs) with 95% confidence intervals.
Results
Approximately 25% of patients in both the COVID-19 (
N
= 787) and non-COVID-19 cohorts (
N
= 77,178) experienced interruptions in TIM therapy. In the non-COVID-19 cohort, the likelihood of being hospitalized was 20% less in patients with uninterrupted versus interrupted TIM use (aOR = 0.80, 95% CI 0.71–0.90). Patients with uninterrupted TIM use had a similar likelihood of an ED visit (aOR = 0.99, 95% CI 0.91–1.08) and respiratory outcome (aOR = 0.97, 95% CI 0.71–1.31) versus patients with interrupted TIM use. The likelihood of having an in-person outpatient visit was 87% greater in patients with uninterrupted versus interrupted TIM use (aOR = 1.87, 95% CI 1.81–1.94). Similar findings were observed in the COVID-19 cohort.
Conclusion
This analysis of real-world claims data showed that uninterrupted TIM use was not associated with an increased likelihood of hospitalizations, ED visits, or negative respiratory outcomes compared to interrupted TIM use among patients with immune-mediated conditions, regardless of COVID-19 diagnosis.
To determine allopurinol treatment patterns and adherence to published standards of care for patients with gout.
This retrospective claims analysis in a managed care database included patients 18 ...years or older, with continuous eligibility for 1 year before and after the start date and 2 or more visits during which the gout disease code (274.xx) was assigned or 1 or more pharmacy prescriptions for a gout-specific medication between January 1, 2000, and December 31, 2002 (intake period). Factors associated with compliance with allopurinol therapy were measured based on the medication possession ratio, and adherence to 2 quality-of-care indicators for gout management was assessed using multivariable logistic regression analysis.
A total of 64.9% of allopurinol users had a modal daily dose or the most commonly observed daily dose of 300 mg/d, median length of therapy was 3 months, and a high proportion of patients had a medication possession ratio of 10% or less. Suggested quality-of-care indicators for gout had low performance: 53% of patients with renal impairment received a modal daily dose of 300 mg or greater, and 83% of patients who started taking allopurinol did not have their serum urate levels measured within 180 days. Patients with gout flares were less likely to be compliant with allopurinol (odds ratio, 0.50; 95% confidence interval, 0.40-0.63). Patients with renal impairment at baseline were 3.2 times more likely to undergo serum urate testing than patients without renal impairment (odds ratio, 3.20; 95% confidence interval, 1.25-8.23).
There was low compliance with allopurinol therapy for treatment of gout. Patients potentially received suboptimal quality of care as measured by serum urate testing and appropriateness of allopurinol dosing in patients with renal impairment.
Ruthenium(III) complexes Ru(bphtpy)(PPh3)Cl3 (bphfpy = diphenylfuranylpyridine derivatives) were synthesized and characterized by LCMS, IR spectroscopy, elemental analysis and magnetic measurements. ...All the complexes were screened for their antibacterial activity in terms of minimum inhibitory concentration against two Gram-positive and three Gram-negative bacterial species. DNA binding study by absorption titration and viscosity measurement shows that complexes bind in an intercalating mode, which is also confirmed by molecular docking. All the complexes were also screened for the DNA nuclease property of pUC19 plasmid DNA. The cytotoxicity study of the synthesized complexes was performed to elucidate the LC50 values to find out the toxicity profile of the complexes.
This study was conducted to evaluate the impact of hot dry, hot humid and comfortable season on physiological, hematological, biochemical, and oxidative stress parameters in Surti buffaloes.
Ten ...lactating Surti buffaloes of similar physiological status were selected. Based on the temperature-humidity index (THI), their natural exposure to the environment was categorized as hot dry (THI1), hot humid (THI2) and moderate winter/comfort season (THI3). Blood/serum samples were collected and analyzed for physiological, hematological, biochemical, and oxidative stress parameters. The results were analyzed using standard statistical methods.
With increase in THI, significant rise in physiological parameters such as respiration rate (RR), hematological parameters such as red blood cell (RBC), hematocrit, hemoglobin (Hb) and mean cell Hb concentration (MCHC), biochemical parameters such as alanine aminotransferase (ALT), Na, K, creatinine, blood urea nitrogen, Mn, Cu and Zn, hormones such as cortisol and oxidative stress parameters such as glutathione peroxidase (GPx), superoxide dismutase (SOD), lipid peroxide (LPO) and total antioxidant status (TAS) and significant decline in glucose, cholesterol and triiodothyronine (T3) was observed.
It was concluded that THI is a sensitive indicator of heat stress and is impacted by ambient temperature more than the relative humidity in buffaloes. Higher THI is associated with significantly increased RR, total RBC count, Hb, hematocrit, MCHC, ALT, urea, sodium, creatinine, triiodothyronine, SOD, GPx, LPO and TAS and with significant decrease in glucose, cholesterol and triiodothyronine (T3).