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BACKGROUND: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. OBJECTIVES: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. METHODS: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. RESULTS: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (nâ=â199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (nâ=â187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. CONCLUSIONS: We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.
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Diabetes Mellitus , Gammaproteobacteria , Gravidez , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Ciprofloxacina/farmacologia , Estudos Transversais , Escherichia coli , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Fatores de Risco , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Resistência a Múltiplos Medicamentos , Atenção Primária à SaúdeRESUMO
PURPOSE: Recurrent cystitis guidelines recommend relying on a local antibiogram or prior urine culture to guide empirical prescribing, yet little data exist to quantify the predictive value of a prior culture. We constructed a urinary antibiogram and evaluated test metrics (sensitivity, specificity, and Bayes' positive and negative predictive values) of a prior gram-negative organism on predicting subsequent resistance or susceptibility among patients with uncomplicated, recurrent cystitis. MATERIALS AND METHODS: We performed a retrospective database study of adults with recurrent, uncomplicated cystitis (cystitis occurring 2 times in 6 months or 3 times in 12 months) from urology or primary care clinics between November 1, 2016, and December 31, 2018. We excluded pregnant females, patients with complicated cystitis, or pyelonephritis. Test metrics were calculated between sequential, paired cultures using standard formulas. RESULTS: We included 597 visits from 232 unique patients wherein 310 (51.2%) visits had a urine culture and 165 had gram-negative uropathogens isolated. Patients with gram-negative uropathogens were mostly females (97%), with a median age of 58.5 years. Our antibiogram found 38.0%, 27.9%, and 5.5% of Escherichia coli isolates had resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin, respectively. Prior cultures (within 2 years) had good predictive value for detecting future susceptibility to first-line agents nitrofurantoin (0.85) and trimethoprim-sulfamethoxazole (0.78) and excellent predictive values (≥0.90) for cefepime, ceftriaxone, cefuroxime, ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin-tazobactam, and imipenem. CONCLUSIONS: Considerable antibiotic resistance was detected among E coli isolates in patients with recurrent, uncomplicated cystitis. Using a prior culture as a guide can enhance the probability of selecting an effective empirical agent.
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Cistite , Infecções Urinárias , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Combinação Trimetoprima e Sulfametoxazol , Nitrofurantoína , Escherichia coli , Estudos Retrospectivos , Teorema de Bayes , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnóstico , Ciprofloxacina , Cistite/tratamento farmacológico , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência BacterianaRESUMO
BACKGROUND: Rising opioid-related death rates have prompted reductions of opioid prescribing, yet limited data exist on population-level associations between opioid prescribing and opioid-related deaths. OBJECTIVE: To evaluate population-level associations between five opioid prescribing measures and opioid-related deaths. DESIGN: An ecological panel analysis was performed using linear regression models with year and commuting zone fixed effects. PARTICIPANTS: People ≥10 years aggregated into 886 commuting zones, which are geographic regions collectively comprising the entire USA. MAIN MEASURES: Annual opioid prescriptions were measured with IQVIA Real World Longitudinal Prescription Data including 76.5% (2009) to 90.0% (2017) of US prescriptions. Prescription measures included opioid prescriptions per capita, percent of population with ≥1 opioid prescription, percent with high-dose prescription, percent with long-term prescription, and percent with opioid prescriptions from ≥3 prescribers. Outcomes were age- and sex-standardized associations of change in opioid prescriptions with change in deaths involving any opioids, synthetics other than methadone, heroin but not synthetics or methadone, and prescription opioids, but not other opioids. KEY RESULTS: Change in total regional opioid-related deaths was positively correlated with change in regional opioid prescriptions per capita (ß=.110, p<.001), percent with ≥1 opioid prescription (ß=.100, p=.001), and percent with high-dose prescription (ß=.081, p<.001). Change in total regional deaths involving prescription opioids was positively correlated with change in all five opioid prescribing measures. Conversely, change in total regional deaths involving synthetic opioids was negatively correlated with change in percent with long-term opioid prescriptions and percent with ≥3 prescribers, but not for persons ≥45 years. Change in total regional deaths in heroin was not associated with change in any prescription measure. CONCLUSIONS: Regional decreases in opioid prescriptions were associated with declines in overdose deaths involving prescription opioids, but were also associated with increases in deaths involving synthetic opioids (primarily fentanyl). Individual-level inferences are limited by the ecological nature of the analysis.
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Analgésicos Opioides , Overdose de Drogas , Humanos , Estados Unidos , Analgésicos Opioides/uso terapêutico , Padrões de Prática Médica , Overdose de Drogas/epidemiologia , Fentanila , MetadonaRESUMO
Context: Rising antibiotic resistance has transcended hospital boundaries and impacted individuals with community acquired urinary tract infections (UTI). Scant data on antibiotic resistance in outpatient settings exists and most studies in the United States (U.S.) have identified predictors of resistance in acute-care settings. Objective: Determine the antibiogram among Escherichia coli isolates and factors associated with ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) resistant gram-negative urinary isolates. Study Design: Retrospective cohort study. Setting: Two primary care, safety-net clinics in Houston, TX between 11/2018 and 3/2020. Population studied: Patients aged 18 and older presenting with provider suspected uncomplicated or complicated UTI. Outcome measures: Resistance and predictors of resistance to UTI-relevant antibiotics. Results: Among 1265 cultures collected, 372 (28.4%) were positive. We detected E. coli (50.3%) and Group B Streptococcus (18.6%) most frequently. Our patient population consisted mostly of Hispanic (75.7%) females (92.5%) born outside the U.S. (67.3%) with a mean age of 47. Among patients with E. coli isolated (n=189), antibiotic resistance was highest to ampicillin (63%), TMP-SMX (44%), ciprofloxacin (31%), and cefazolin (30%); no or low resistance against amikacin (0%), fosfomycin (0%), and nitrofurantoin (2.7%) was detected. Approximately 12% of E. coli isolates were extended-spectrum beta-lactamase positive. Having a prior UTI caused by a TMP-SMX resistant gram-negative organism and being born outside the U.S increased the odds of TMP-SMX resistance by 3.71 (95% confidence interval: 1.6-9.2) and 3.08 (95% CI: 1.6-6.3), respectively. Having a complicated UTI (odds ratio (OR): 3.58; 95% CI: 1.1-12.1), prior fluoroquinolone use (OR: 6.81; 95% CI: 1.7-34.1) and a prior UTI with ciprofloxacin resistance (OR: 7.84; 95% CI: 3.2-20.7) increased the odds of having a ciprofloxacin resistance. Conclusion: The Infectious Disease Society of America cautions against prescribing an antibiotic if regional resistance exceeds 20%. We constructed an antibiogram and found resistance surpassed this threshold for TMP-SMX and ciprofloxacin and identified factors associated with resistance to these agents. Assessing these characteristics during clinical decision making may improve antibiotic-organism susceptibility concordance in primary care.
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Infecções por Escherichia coli , Infecções Urinárias , Feminino , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Masculino , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Escherichia coli , Estudos Retrospectivos , Pacientes Ambulatoriais , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Farmacorresistência Bacteriana , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
Although a substantial body of work has investigated drivers of tie formation, there is growing interest in understanding why relationships decay or dissolve altogether. The networks literature has tended to conceptualize tie decay as driven by processes similar to those underlying tie formation. Yet information that is revealed through ongoing interactions can exert different effects on tie formation and tie decay. This paper investigates how tie decay and tie formation processes differ by focusing on contentious practices. To the extent that information about dissimilarities in contentious practices is learned through ongoing interactions, it can exert diverging effects on tie formation and tie decay. Using a longitudinal data set of 141,543 physician dyads, we find that differences in contentious prescribing led ties to weaken or dissolve altogether but did not affect tie formation. The more contentious the practice and the more information available about the practice, the stronger the effect on tie decay and dissolution. Collectively, these findings contribute to a more nuanced understanding of relationship evolution as an unfolding process through which deeper-level differences are revealed and shape the outcome of the tie.
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BACKGROUND: Investigating primary care provider (PCP)-team communication can provide insight into how colleagues work together to become high-functioning teams more able to address an increasingly complex set of tasks associated with chronic disease management. OBJECTIVE: To assess how PCP communication with their care team relates to patients' health. RESEARCH DESIGN: Longitudinal study of how 3 aspects of PCP-care team communication-participation, time spent listening, and uninterrupted speaking length-relate to disease management of patients with hypertension or diabetes, and the effect of these team communication behaviors on PCP-patient communication as a pathway by which this relationship might exist. We used multilevel regression models. SUBJECTS: Twenty-seven PCPs and 98 team members, and 18,067 patients with hypertension and 8354 patients with diabetes affiliated with a federally qualified health center with 12 practice sites. MEASURES: Primary data on communication collected using sociometric sensors worn by PCPs and team members, patient-PCP communication data collected with surveys, and patient health, PCP and patient characteristics extracted from electronic records. RESULTS: PCPs participated in 75% of care team conversations, spent 56% of conversation time listening, and had an average uninterrupted speaking length of 2.42 seconds. PCP participation, listening, and length of uninterrupted speaking time were associated with significantly higher odds that their patients had controlled hypertension and diabetes and improvements in disease control over time. PCP-patient communication mediates this relationship. CONCLUSIONS: PCP-team communication is associated with patient health management. How team members speak with one another may be as important as the content of their communication.
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Gerenciamento Clínico , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente/normas , Atenção Primária à Saúde/métodos , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/estatística & dados numéricos , Atenção Primária à Saúde/normas , Atenção Primária à Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde/normas , Qualidade da Assistência à Saúde/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Mycoplasmas primarily cause respiratory or urogenital tract infections impacting avian, bovine, canine, caprine, murine, and reptilian hosts. In animal husbandry, mycoplasmas cause reduced feed-conversion, decreased egg production, arthritis, hypogalactia or agalactia, increased condemnations, culling, and mortality in some cases. Antibiotics reduce transmission and mitigate clinical signs; however, concerning levels of antibiotic resistance in Mycoplasma gallisepticum and M. capricolum isolates exist. To address these issues, we evaluated the minimum inhibitory concentrations (MICs) of halogenated phenazine and quinoline compounds, an N-arylated NH125 analogue, and triclosan against six representative veterinary mycoplasmas via microbroth or agar dilution methods. Thereafter, we evaluated the minimum bactericidal concentration (MBC) of efficacious drugs. RESULTS: We identified several compounds with MICs ≤25 µM against M. pulmonis (n = 5), M. capricolum (n = 4), M. gallisepticum (n = 3), M. alligatoris (n = 3), M. agassizii (n = 2), and M. canis (n = 1). An N-arylated NH125 analogue, compound 21, served as the most efficacious, having a MIC ≤25 µM against all mycoplasmas tested, followed by two quinolines, nitroxoline (compound 12) and compound 20, which were effective against four and three mycoplasma type strains, respectively. Nitroxoline exhibited bactericidal activity among all susceptible mycoplasmas, and compound 21 exhibited bactericidal activity when the MBC was able to be determined. CONCLUSIONS: These findings highlight a number of promising agents from novel drug classes with potential applications to treat veterinary mycoplasma infections and present the opportunity to evaluate preliminary pharmacokinetic indices using M. pulmonis in rodents as an animal model of human infection.
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Antibacterianos/farmacologia , Imidazóis/farmacologia , Mycoplasma/efeitos dos fármacos , Fenazinas/farmacologia , Quinolinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against Ureaplasma species and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis, and Ureaplasma urealyticum) using a validated broth microdilution or agar dilution method. Among 72 Ureaplasma species clinical isolates, nitroxoline proved most effective (MIC90, 6.25 µM), followed by an N-arylated NH125 analogue (MIC90, 12.5 µM). NH125 and its analogue had significantly higher MICs against U. urealyticum isolates than against U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium, with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma species isolates.
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Antibacterianos/farmacologia , Imidazóis/farmacologia , Mycoplasma/efeitos dos fármacos , Fenazinas/farmacologia , Quinolinas/farmacologia , Ureaplasma urealyticum/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Mycoplasma/classificação , Mycoplasma/isolamento & purificação , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Ureaplasma/tratamento farmacológico , Ureaplasma urealyticum/isolamento & purificaçãoRESUMO
Urinary tract infections (UTIs) affect nearly 20% of women age 15 to 29 and account for an estimated $3.5 billion in costs. Antibiotic resistance prolongs UTI treatment, and resistance profiles vary regionally. This regional variation is an important consideration in guiding empirical treatment selection. Regional studies in the United States have identified tetracycline resistance in over one-third of Ureaplasma species isolates, but no studies have evaluated antibiotic resistance levels in college-aged women with a first-time UTI. We tested a panel of antibiotics and determined the MICs of Ureaplasma species (60 U. parvum and 13 U. urealyticum) and 10 Mycoplasma hominis isolates obtained from urine from college-aged women with a first-time UTI. Low antibiotic resistance was found in this population of women with a first-time UTI. All M. hominis and U. urealyticum isolates were sensitive. However, two U. parvum isolates were resistant, with one to levofloxacin (MIC, 4 µg/ml) and one to tetracycline (MIC, 8 µg/ml). For the Ureaplasma spp., the MIC90s were highest against gentamicin (21 µg/ml) and lowest against doxycycline (0.25 µg/ml). In a comparison of MIC levels between Ureaplasma spp., U. urealyticum had significantly higher MICs against each antibiotic except doxycycline. For the resistant isolates, the genetic mechanisms of resistance were determined. PCR amplification identified tetM to be present in the tetracycline-resistant isolate and an S83W mutation within the parC gene of the quinolone-resistant isolate. To our knowledge, this study is the first to provide molecular and phenotypic evidence of the S83W parC mutation conferring levofloxacin resistance in U. parvum isolated from a patient in the United States.
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Antibacterianos/farmacologia , Mycoplasma hominis/efeitos dos fármacos , Resistência a Tetraciclina/genética , Ureaplasma/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , DNA Topoisomerase IV/genética , Doxiciclina/farmacologia , Feminino , Gentamicinas/farmacologia , Humanos , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis/isolamento & purificação , Estudos Prospectivos , Tetraciclina/farmacologia , Estados Unidos , Ureaplasma/classificação , Ureaplasma/isolamento & purificação , Infecções por Ureaplasma/tratamento farmacológico , Infecções por Ureaplasma/microbiologia , Infecções Urinárias/microbiologia , Urina/microbiologia , Adulto JovemRESUMO
BACKGROUND: Displaced tibial spine fractures are frequently treated with surgical reduction and fixation, but no comparison studies have been performed. This study was undertaken to compare fragment reduction and adverse outcomes between open arthrotomy [open reduction and internal fixation (ORIF)], arthroscopy [arthroscopic-assisted internal fixation (AAIF)], and closed management [closed management and casting (CMC)] of pediatric tibial spine fractures. METHODS: A retrospective review of children treated for displaced tibial spine fractures from 2003 to 2011 was performed after categorizing into the 3 treatment groups. Demographics, mechanism of injury, radiographic measures (plain film and computed tomography), treatment, duration of immobilization and follow-up, final range of motion, and complications were recorded. Families were contacted to obtain long-term Lysholm scores, return to activity, pain, and satisfaction with treatment. RESULTS: Seventy-six children (mean age, 12.4 y) met criteria with 29 ORIF, 28 AAIF, and 19 CMC. Radiographic measurements between x-ray and computed tomography scans found a mean error of 1 mm (SD=1.33 mm; inter-class coefficient = 0.977, P < 0.001). Initial fracture displacement was similar between AAIF and ORIF, 10.3 ± 4.4 mm and 10.8 ± 3.9 mm; but, less in CMC group (5.3 ± 2.6 mm). The mean reduction amount was 8.6 ± 4.7, 9.1 ± 4.0, and 2.3 ± 2.6 mm, respectively. A Bonferroni post hoc analysis revealed a difference between surgical and nonoperative reduction (P < 0.001), but not between AAIF and ORIF (P=0.9). Arthrofibrosis occurred with equal frequency in surgical cohorts (AAIF 12.5%, ORIF 11.1%), compared with none in the CMC group. Yet, the CMC group had a 16.7% risk for reoperation secondary to instability, loose bodies, or impingement. Twenty-four percent of each cohort was available (at mean 6.0 y) for interview with mean (median) Lysholm score: ORIF 97.4 (99), AAIF 95 (100), and CMC 86 (97.5), P = 0.35. CONCLUSIONS: Open or arthroscopic treatment of displaced tibial spine fractures affords a better reduction than closed management, but with higher risk for arthrofibrosis. Closed management may be successful when displacement is < 5 mm, and advanced imaging may not be necessary to delineate the amount of displacement.
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Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Adolescente , Análise de Variância , Artroscopia/métodos , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Luxações Articulares/cirurgia , Masculino , Amplitude de Movimento Articular , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Buprenorfina/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos/tendências , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Distribuição por Sexo , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: This study estimates associations of regional change in opioid prescribing with total suicide deaths and suicide overdose deaths involving opioids. METHODS: A panel analysis was performed with 2009-2017 U.S. national IQVIA Longitudinal Prescription Database data and National Center for Health Statistics mortality data aggregated into commuting zones (N=886), which together span the United States. Opioid prescription exposures included opioid prescriptions per capita and percentages of patients with any opioid prescription, with high-dose prescriptions (>120 mg of morphine equivalents), with long-term prescriptions (≥60 consecutive days), and with prescriptions from three or more prescribers. Linear regression models were used with year and commuting zone fixed effects. RESULTS: Suicide deaths were significantly positively associated with opioid prescriptions per capita (ß=0.045), having any opioid prescription (ß=0.069), having high-dose prescriptions (ß=0.024), having long-term prescriptions (ß=0.028), and having three or more opioid prescribers (ß=0.046). Similar significant associations were observed between each of the five opioid prescription measures and suicide overdose deaths involving opioids (ß range, 0.029-0.042). However, opioid prescriptions per capita, having any opioid prescription, and having three or more opioid prescribers were each negatively associated with unintentional opioid-related deaths in people in the 10- to 24-year and 25- to 44-year age groups. CONCLUSIONS: In this retrospective study of U.S. commuting zone-level opioid prescriptions and mortality, regional decreases in opioid prescriptions were consistently associated with declines in total suicide deaths, including suicide overdose deaths involving opioids. For some opioid prescribing measures, negative associations were observed with unintentional overdose deaths involving opioids among younger people. Individual-level inferences are limited by the ecological nature of the analysis.
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Overdose de Drogas , Suicídio , Humanos , Estados Unidos/epidemiologia , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Padrões de Prática MédicaRESUMO
Carbohydrates are chemically and structurally diverse biomolecules, serving numerous and varied roles in agricultural ecosystems. Crops and horticulture products are inherent sources of carbohydrates that are consumed by humans and non-human animals alike; however carbohydrates are also present in other agricultural materials, such as soil and compost, human and animal tissues, milk and dairy products, and honey. The biosynthesis, modification, and flow of carbohydrates within and between agricultural ecosystems is intimately related with microbial communities that colonize and thrive within these environments. Recent advances in -omics techniques have ushered in a new era for microbial ecology by illuminating the functional potential for carbohydrate metabolism encoded within microbial genomes, while agricultural glycomics is providing fresh perspective on carbohydrate-microbe interactions and how they influence the flow of functionalized carbon. Indeed, carbohydrates and carbohydrate-active enzymes are interventions with unrealized potential for improving carbon sequestration, soil fertility and stability, developing alternatives to antimicrobials, and circular production systems. In this manner, glycomics represents a new frontier for carbohydrate-based biotechnological solutions for agricultural systems facing escalating challenges, such as the changing climate.
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Carboidratos , Microbiota , Animais , Carboidratos/química , Metabolismo dos Carboidratos , Agricultura , Solo/químicaRESUMO
Few studies have harnessed social media to explore patients' experiences with urinary tract infection (UTI); therefore, we captured UTI experiences and future research suggestions through a Twitter-disseminated survey. The survey posed three qualitative questions inquiring about the impact of UTIs, greatest UTI management hurdle, and research suggestions. We also asked participants to rate how seriously others perceive UTIs and the importance of UTIs in their life (scale: 1-100 (highest)). The study period spanned from January to June 2021. Coding was performed in duplicate, followed by thematic analysis. Of 466 participants from 22 countries, 128 considered their UTIs recurrent (n = 43) or chronic (n = 85). Six major themes emerged: UTIs drastically impact (1) physical and (2) mental health and (3) cause severe limitations in life activities. Patients reported (4) negative clinician interactions and perceived inadequate care, (5) a lack of knowledge and awareness surrounding UTIs, and (6) research gaps in UTI diagnostics and treatment. The participants considered UTIs extremely important (median: 100, IQR: 90-100), but characterized others' perceptions of them as less serious (median: 20, IQR: 10-30). Our survey revealed a patient population struggling with UTIs, particularly chronic UTIs. Our findings highlight perceived shortcomings in current UTI treatment and diagnostics.
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Objectives: We characterized antibiotic prescribing patterns and management practices among recurrent urinary tract infection (rUTI) patients, and we identified factors associated with lack of guideline adherence to antibiotic choice, duration of treatment, and urine cultures obtained. We hypothesized that prior resistance to nitrofurantoin or trimethoprim-sulfamethoxazole (TMP-SMX), shorter intervals between rUTIs, and more frequent rUTIs would be associated with fluoroquinolone or ß-lactam prescribing, or longer duration of therapy. Methods: This study was a retrospective database study of adult women with International Classification of Diseases, Tenth Revision (ICD-10) cystitis codes meeting American Urological Association rUTI criteria at outpatient clinics within our academic medical center between 2016 and 2018. We excluded patients with ICD-10 codes indicative of complicated UTI or pyelonephritis. Generalized estimating equations were used for risk-factor analysis. Results: Among 214 patients with 566 visits, 61.5% of prescriptions comprised first-line agents of nitrofurantoin (39.7%) and TMP-SMX (21.5%), followed by second-line choices of fluoroquinolones (27.2%) and ß-lactams (11%). Most fluoroquinolone prescriptions (86.7%), TMP-SMX prescriptions (72.2%), and nitrofurantoin prescriptions (60.2%) exceeded the guideline-recommended duration. Approximately half of visits lacked a urine culture. Receiving care through urology via telephone was associated with receiving a ß-lactam (adjusted odds ratio [aOR], 6.34; 95% confidence interval [CI], 2.58-15.56) or fluoroquinolone (OR, 2.28; 95% CI, 1.07-4.86). Having >2 rUTIs during the study period and seeking care from a urology practice (RR, 1.28, 95% CI, 1.15-1.44) were associated with longer antibiotic duration. Conclusions: We found low guideline concordance for antibiotic choice, duration of therapy and cultures obtained among rUTI patients. These factors represent new targets for outpatient antibiotic stewardship interventions.
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BACKGROUND: Chart reviews often fall short of determining what drove antibiotic treatment of asymptomatic bacteriuria (ASB). To overcome this shortcoming, we searched providers' free-text for documentation of their decision-making and for misleading signs and symptoms that may trigger unnecessary treatment of ASB. METHODS: We reviewed a random sample of 10 positive urine cultures per month, per facility, from patients in acute or long-term care wards at 8 Veterans Affairs facilities. Cultures were classified as urinary tract infection (UTI) or ASB, and as treated or untreated. Charts were searched for 13 potentially misleading symptoms, and free-text documentation of providers' decision-making was classified into 5 categories. We used generalized estimating equations logistic regression to identify factors associated with ASB treatment. RESULTS: One hundred fifty-eight (27.5%) of 575 ASB cases were inappropriately treated with antibiotics. Significant factors associated with inappropriate treatment included: abdominal pain, falls, decreased urine output, urine characteristics, abnormal vital signs, laboratory values, and voiding issues. Providers prescribed an average of 1.4 antimicrobials to patients with ASB, with cephalosporins (41%) and fluoroquinolones (21%) being the most common classes prescribed. CONCLUSIONS: Chart reviews of providers' decision-making highlighted new factors associated with inappropriate ASB treatment. These findings can help design antibiotic stewardship interventions for ASB.
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BACKGROUND: Antimicrobial resistance is a global health threat. To slow resistance and preserve antibiotics, stewardship interventions are increasingly promoted and mandated. Urine cultures are the most common microbiological test in the outpatient setting. Contamination most likely occurs during urine collection from surrounding vaginal, perineal, and epidermal flora. Sample contamination can lead to incorrect diagnosis, unnecessary or inappropriate treatment, poor patient outcomes, and higher costs. Therefore, ensuring proper collection of urinary samples serves as a prime diagnostic stewardship target, one that international nursing societies increasingly endorse as an opportunity for nurse involvement. OBJECTIVES: Determine the prevalence, predictors, and antibiotic prescribing associated with contaminated urine cultures in primary care clinics. DESIGN: Cross-sectional study. SETTING: Two adult safety-net clinics in Houston, Texas. PARTICIPANTS: 1265 clinical encounters among 1114 primary care patients. METHODS: We reviewed charts from office visits among patients who had a urine culture ordered between November 2018 and March 2020. Patient demographics, culture results and prescription orders were captured for each visit. Culture results were defined as no growth, contaminated (i.e., mixed flora, non-uropathogens, or ≥3 bacterial species isolated), or low-count (102-105 colony forming units (CFU)/mL) or high-count (>105â¯CFU/mL) uropathogen-positive. We performed multinomial logistic regression to identify predictors independently associated with contaminated cultures. RESULTS: Our study evaluated 1265 cultures from 1114 patients that were primarily female (84â¯%), of Hispanic/Latino (74.4â¯%) or Black/African American (18.9â¯%) race/ethnicity with a mean age of 43â¯years. Out of 1265 urine cultures, 264 (20.9â¯%) had no growth, 694 (54.9â¯%) were contaminated, 159 (12.6â¯%) were low-count positive, and 148 (11.7â¯%) were high-count positive. Female sex, pregnancy, and obesity were associated with contaminated cultures (multinomial adjusted odds ratios: 15.89, 14.34, 1.93, respectively; 95â¯% confidence intervals: 10.25-24.61, 8.03-25.61, 1.32-2.81, respectively). Antibiotic prescribing was significantly higher among symptomatic patients with contaminated cultures compared to those with no growth. CONCLUSION: Urine culture contamination occurred frequently in our clinics, and obesity, female sex and pregnancy were independent risk factors for contamination. The association of pregnancy and contamination is particularly concerning as pregnant females are routinely screened and treated for asymptomatic bacteriuria in the United States. Culture contamination may obscure underlying uropathogens, leading to pyelonephritis or potential neonatal infection if untreated. Conversely, overtreatment of false positive bacteriuria could lead to adverse effects from antibiotics and increased risk for antibiotic resistance. As nurses play a prominent role in patient education, diagnostic stewardship interventions may want to utilize nurses' educational capabilities to improve urine culture collection. TWEETABLE ABSTRACT: 55â¯% of urine cultures collected in primary care clinics were contaminated, revealing a major opportunity for nurse-driven diagnostic stewardship interventions.
Assuntos
Bacteriúria , Infecções Urinárias , Adulto , Antibacterianos/uso terapêutico , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Bacteriúria/microbiologia , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Obesidade/complicações , Gravidez , Prevalência , Atenção Primária à SaúdeRESUMO
Amino acids 50-77 (p28) of azurin, a 128 aa cupredoxin isolated from Pseudomonas aeruginosa, is essentially responsible for azurin's preferential penetration of cancer cells. We now report that p28 also preferentially penetrates human umbilical vein endothelial cells (HUVEC), co-localized with caveolin-1 and VEGFR-2, and inhibits VEGF- and bFGF-induced migration, capillary tube formation and neoangiogenesis in multiple xenograft models. The antiangiogenic effect of p28 in HUVEC is associated with a dose-related non-competitive inhibition of VEGFR-2 kinase activity. However, unlike other antiangiogenic agents that inhibit the VEGFR-2 kinase, p28 decreased the downstream phosphorylation of FAK and Akt that normally precedes cellular repositioning of the cytoskeletal (F-actin), focal adhesion (FAK and paxillin), and cell to cell junction protein PECAM-1, inhibiting HUVEC motility and migration. The decrease in pFAK and pAkt levels suggests that p28 induces a pFAK-mediated loss of HUVEC motility and migration and a parallel Akt-associated reduction in cell matrix attachment and survival. This novel, direct antiangiogenic effect of p28 on endothelial cells may enhance the cell cycle inhibitory and apoptotic properties of this prototype peptide on tumor cell proliferation as it enters a Phase II clinical trial.
Assuntos
Antineoplásicos/farmacocinética , Azurina/farmacologia , Peptídeos Penetradores de Células/farmacologia , Células Endoteliais/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Actinas/metabolismo , Animais , Antineoplásicos/química , Azurina/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Peptídeos Penetradores de Células/química , Ensaios Clínicos Fase II como Assunto , Células Endoteliais/patologia , Adesões Focais/metabolismo , Humanos , Camundongos , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fragmentos de Peptídeos/química , Fosforilação/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pseudomonas aeruginosa/química , Veias Umbilicais/metabolismo , Veias Umbilicais/patologiaRESUMO
The prevalence of autism has increased precipitously-roughly 10-fold in the past 40 years-yet no one knows exactly what caused this dramatic rise. Using a large and representative dataset that spans the California birth cohorts from 1992 through 2000, we examine individual and community resources associated with the likelihood of an autism diagnosis over time. This allows us to identify key social factors that have contributed to increased autism prevalence. While individual-level factors, such as birth weight and parental education, have had a fairly constant effect on likelihood of diagnosis over time, we find that community-level resources drive increased prevalence. This study suggests that neighborhoods dynamically interact with the people living in them in different ways at different times to shape health outcomes. By treating neighborhoods as dynamic, we can better understand the changing socioeconomic gradient of autism and the increase in prevalence.
RESUMO
OBJECTIVE: The authors examined changes in buprenorphine treatment following Medicaid expansion, including the contribution of Medicaid-financed prescriptions. METHODS: Buprenorphine pharmacy claims for patients were identified in the 2012-2018 IQVIA Longitudinal Prescription Data (LRx) data set, including 79.8% of U.S. retail prescriptions in 2012, increasing to 92.0% in 2018. A cohort analysis was used to assess the mean number of patients in a yearly quarter filling one or more buprenorphine prescriptions during preexpansion (2012-2013) and postexpansion (2014-2018) periods in expansion and nonexpansion states. Interrupted time-series analysis estimated associations of Medicaid expansion period with change in Medicaid-financed treatment. Separate analyses evaluated changes in duration and dose of new treatment episodes focused on mean quarterly number of patients treated with buprenorphine and proportions of new treatment episodes ≥180 days long and with ≥16 mg/day. RESULTS: Between preexpansion and postexpansion, the mean quarterly number of patients taking buprenorphine increased by 93,300 in expansion states and by 84,960 in nonexpansion states. Corresponding changes for Medicaid-financed patients were 28,760 and 4,050, respectively. The fastest growth in Medicaid-financed treatment occurred among patients ages 25-44. Among new Medicaid-financed treatment episodes, little change was found in the proportion reaching the 180-day threshold, and declines were observed in the proportion receiving ≥16 mg/day. CONCLUSIONS: The findings are consistent with previous research indicating that Medicaid expansion has increased Medicaid-financed buprenorphine treatment. However, because of offsetting changes in other payment groups, the overall increase in expansion states was similar to the increase in nonexpansion states.