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1.
J Gen Intern Med ; 39(4): 566-572, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38129617

RESUMO

BACKGROUND: As patient-initiated messaging rises, identifying variation in message volume and its relationship to clinician workload is essential. OBJECTIVE: To describe the association between variation in message volume over time and time spent on the electronic health record (EHR) outside of scheduled hours. DESIGN: Retrospective cohort study. PARTICIPANTS: Primary care clinicians at Cleveland Clinic Health System. MAIN MEASURES: We categorized clinicians according to their number of quarterly incoming medical advice messages (i.e., message volume) between January 2019 and December 2021 using group-based trajectory modeling. We assessed change in quarterly messages and outpatient visits between October-December 2019 (Q4) and October-December 2021 (Q12). The primary outcome was time outside of scheduled hours spent on the EHR. We used mixed effects logistic regression to describe the association between incoming portal messages and time spent on the EHR by clinician messaging group and at the clinician level. KEY RESULTS: Among the 150 clinicians, 31% were in the low-volume group (206 messages per quarter per clinician), 47% were in the moderate-volume group (505 messages), and 22% were in the high-volume group (840 messages). Mean quarterly messages increased from 340 to 695 (p < 0.001) between Q4 and Q12; mean quarterly outpatient visits fell from 711 to 575 (p = 0.005). While time spent on the EHR outside of scheduled hours increased modestly for all clinicians, this did not significantly differ by message group. Across all clinicians, each additional 10 messages was associated with an average of 12 min per quarter of additional time spent on the EHR (p < 0.001). CONCLUSIONS: Message volume increased substantially over the study period and varied by group. While messages were associated with additional time spent on the EHR outside of scheduled hours, there was no significant difference in time spent on the EHR between the high and low message volume groups.


Assuntos
Registros Eletrônicos de Saúde , Portais do Paciente , Humanos , Estudos Retrospectivos , Carga de Trabalho , Atenção Primária à Saúde
2.
Diabetes Obes Metab ; 26(5): 1687-1696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38287140

RESUMO

AIM: To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2015 to 30 June 2023, in a large health system in Ohio and Florida. Adults with a body mass index ≥30 kg/m2 who attended ≥1 weight-management programme or had an initial AOM prescription between 1 July 2015 and 31 December 2022, were included. The main measures were a prescription for an AOM (naltrexone-bupropion, orlistat, phentermine-topiramate, liraglutide 3.0 mg and semaglutide 2.4 mg) and an AOM fill during the study follow-up. RESULTS: We identified 50 678 adults, with a mean body mass index of 38 ± 8 kg/m2 and follow-up of 4.7 ± 2.4 years. Only 8.0% of the cohort had AOM prescriptions and 4.4% had filled prescriptions. In the multivariable analyses, being a man, Black, Hispanic and other race/ethnicity (vs. White), Medicaid, traditional Medicare, Medicare Advantage, self-pay and other insurance types (vs. private insurance) and fourth quartile of the area deprivation index (vs. first quartile) were associated with lower odds of a new prescription. Hispanic ethnicity, being a man, Medicaid, traditional Medicare and Medicare Advantage insurance types, liraglutide and orlistat (vs. naltrexone-buproprion) were associated with lower odds of AOM fill, while phentermine-topiramate was associated with higher odds. Among privately insured individuals, the insurance carrier was associated with both the odds of AOM prescription and fill. CONCLUSIONS: Significant disparities exist in access to AOM both at the prescribing stage and getting the prescription filled based on patient characteristics and insurance type.


Assuntos
Fármacos Antiobesidade , Medicare Part C , Idoso , Adulto , Humanos , Estados Unidos/epidemiologia , Orlistate/uso terapêutico , Estudos Retrospectivos , Topiramato , Naltrexona/uso terapêutico , Liraglutida/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Fentermina
3.
Immunology ; 170(1): 154-166, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37219921

RESUMO

Monocyte-derived macrophages contribute centrally to immune protection in Mycobacterium tuberculosis infection and changes in monocyte phenotype characterize immunopathology in tuberculosis patients. Recent studies highlighted an important role of the plasma milieu in tuberculosis immunopathology. Here, we investigated monocyte pathology in patients with acute tuberculosis and determined tuberculosis plasma milieu effects on phenotype as well as cytokine signalling of reference monocytes. Patients with tuberculosis (n = 37) and asymptomatic contacts (controls n = 35) were recruited as part of a hospital-based study in the Ashanti region of Ghana. Multiplex flow cytometry phenotyping of monocyte immunopathology was performed and effects of individual blood plasma samples on reference monocytes prior to and during treatment were characterized. Concomitantly, cell signalling pathways were analysed to elucidate underlying mechanisms of plasma effects on monocytes. Multiplex flow cytometry visualization characterized changes in monocyte subpopulations and detected higher expression of CD40, CD64 and PD-L1 in monocytes from tuberculosis patients as compared to controls. Aberrant expression normalized during anti-mycobacterial treatment and also CD33 expression decreased markedly. Notably, higher CD33, CD40 and CD64 expression was induced in reference monocytes when cultured in the presence of plasma samples from tuberculosis patients as compared to controls. STAT signalling pathways were affected by the aberrant plasma milieu and higher levels of STAT3 and STAT5 phosphorylation was found in tuberculosis plasma-treated reference monocytes. Importantly, high pSTAT3 levels were associated with high CD33 expression and pSTAT5 correlated with CD40 as well as CD64 expression. These results suggested plasma milieu effects with potential implications on monocyte phenotype and function in acute tuberculosis.


Assuntos
Monócitos , Tuberculose , Humanos , Macrófagos , Antígenos CD40 , Plasma
4.
J Gen Intern Med ; 38(12): 2742-2748, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36997793

RESUMO

BACKGROUND: Early recognition and treatment of bacteremia can be lifesaving. Fever is a well-known marker of bacteremia, but the predictive value of temperature has not been fully explored. OBJECTIVE: To describe temperature as a predictor of bacteremia and other infections. DESIGN: Retrospective review of electronic health record data. SETTING: A single healthcare system comprising 13 hospitals in the United States. PATIENTS: Adult medical patients admitted in 2017 or 2018 without malignancy or immunosuppression. MAIN MEASURES: Maximum temperature, bacteremia, influenza and skin and soft tissue (SSTI) infections based on blood cultures and ICD-10 coding. KEY RESULTS: Of 97,174 patients, 1,518 (1.6%) had bacteremia, 1,392 (1.4%) had influenza, and 3,280 (3.3%) had an SSTI. There was no identifiable temperature threshold that provided adequate sensitivity and specificity for bacteremia. Only 45% of patients with bacteremia had a maximum temperature ≥ 100.4˚F (38˚C). Temperature showed a U-shaped relationship with bacteremia with highest risk above 103˚F (39.4˚C). Positive likelihood ratios for influenza and SSTI also increased with temperature but showed a threshold effect at ≥ 101.0 ˚F (38.3˚C). The effect of temperature was similar but blunted for patients aged ≥ 65 years, who frequently lacked fever despite bacteremia. CONCLUSIONS: The majority of bacteremic patients had maximum temperatures below 100.4 ˚F (38.0˚C) and positive likelihood ratios for bacteremia increased with high temperatures above the traditional definition of fever. Efforts to predict bacteremia should incorporate temperature as a continuous variable.


Assuntos
Bacteriemia , Influenza Humana , Adulto , Humanos , Temperatura , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Febre/diagnóstico , Sensibilidade e Especificidade , Estudos Retrospectivos
5.
Dig Dis Sci ; 67(9): 4387-4394, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35034240

RESUMO

BACKGROUND: Helicobacter pylori eradication is associated with reduced gastric cancer and peptic ulcer disease incidence and mortality. Factors influencing patients' experiences surrounding H. pylori diagnosis and management are not well-described. Current patient perceptions can influence adherence to treatment, and also their anxieties related to this potentially carcinogenic condition. The objective of this study was to understand the patient experience surrounding H. pylori management and to qualitatively construct a contextual framework to inform and guide providers who manage patients with H. pylori infection. METHODS: We conducted a qualitative analysis using a focus group and one-on-one telephone interviews. An iterative inductive/deductive approach was applied to recorded transcripts to identify and hierarchically order themes. Patient experience was defined according to major themes within a structured health behavior framework. RESULTS: Theme saturation was achieved with thirteen participants (mean age 50.4 years; 62% female; 38% non-Hispanic white). Qualitative analysis yielded a total of 987 codes that resulted in five major themes related to the patient H. pylori experience: context of decision-making; health beliefs; barriers experienced; cues to action; and impact of new knowledge. These themes aligned with the Health Behavior Model framework. Participants were motivated to treat H. pylori. However, the experience was more often perceived negatively versus positively. The perceived patient-provider interaction contributed most prominently to the negative experience compared to other patient experiences, including treatment-related side effects. Internal cues, including symptoms and fear of cancer, modified participants' perceptions and motivation to accept treatment. CONCLUSIONS: Patient experiences related to H. pylori management are predominantly negative. Increasing providers' awareness about patients' values, beliefs, anxieties, and expectations surrounding H. pylori diagnosis/treatment may improve provider-patient communication and, ideally, related outcomes.


Assuntos
Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/complicações
6.
Clin Med Res ; 17(3-4): 72-81, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31582419

RESUMO

OBJECTIVE: Surveillance of antimicrobial resistance patterns on a local level can reveal paradigms not obvious on a regional or national scale. Data collection from this perspective may potentially impact local prescribing patterns and empiric treatment guidelines. The objective of this study was to establish a baseline Staphylococcus aureus antibiogram for the state of Wisconsin and to elucidate potential geographic and demographic factors associated with antimicrobial resistance. DESIGN: Multi-center laboratory surveillance, with testing at a single site utilizing standardized media and susceptibility testing protocols. METHODS: 309 isolates of clinically-significant S. aureus were collected from hospital microbiology laboratories across Wisconsin in 2018, with distribution across seven geographic regions. Each isolate was tested using reference broth microdilution methods against a panel of 15 antimicrobial agents. Percentage susceptibility data, as well as median and 90th percentile minimum inhibitory concentration (MIC) values, were computed for each antimicrobial agent as a function of geographic region or demographic category. RESULTS: Increased resistance to penicillin (≥ 86.0% of isolates), erythromycin (≥ 56.8%), cefoxitin (≥ 45.5%), levofloxacin (≥ 25.0%), and clindamycin (≥ 20.5%) was observed in the Southcentral, Lake Winnebago, and Southeast regions of Wisconsin. In addition, isolates phenotypically classified as methicillin-resistant S. aureus (MRSA) were found to have increased rates of resistance to clindamycin, erythromycin, and levofloxacin as compared to S. aureus isolates susceptible to cefoxitin. S. aureus isolates demonstrated nearly 100% in vitro susceptibility to ceftaroline, dalbavancin, and telavancin. Statewide S. aureus isolates exhibited a vancomycin MIC90 of 1 µg/mL. S. aureus isolates from patients aged 20-39 years were more likely to demonstrate cefoxitin resistance when compared to other age groups (P ≤ 0.03), while isolates from patients ≥ 80 years were more likely to exhibit resistance to levofloxacin and clindamycin (P ≤ 0.046). CONCLUSIONS: Several antimicrobial agents continue to demonstrate in vitro efficacy against clinical isolates of S. aureus (including MRSA) throughout Wisconsin, including three agents with recently-published susceptibility testing guidelines. However, continued surveillance efforts may be necessary in the Lake Winnebago, Southeast, and Southcentral regions to further assess higher rates of resistance to a number of antimicrobial agents.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Wisconsin/epidemiologia , Adulto Jovem
7.
PLoS Biol ; 13(6): e1002169, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26042786

RESUMO

Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen-host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins. We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host-pathogen interaction system.


Assuntos
Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Evolução Biológica , Interações Hospedeiro-Patógeno/genética , Receptores de Superfície Celular/genética , Seleção Genética , Animais , Bacillus thuringiensis/patogenicidade , Caenorhabditis elegans/microbiologia , Genoma Bacteriano , Genômica , Genótipo , Proteínas de Insetos , Fenótipo , Virulência
8.
J Adolesc Health ; 75(2): 242-248, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38739054

RESUMO

PURPOSE: Driving after drinking is a preventable threat to public health. We examined the prospective association of adolescent-reported parental monitoring knowledge (PMK) with recurrent driving after drinking in emerging adulthood. METHODS: We analyzed six annual rounds (1-4, 6, 11) of the National Longitudinal Survey of Youth 1997 with a sample of 5,261 participants. PMK variables were created to recategorize parental monitoring measures by age of the youth. Recurrent driving after drinking was measured in 2002 and 2007 and dichotomized. Unadjusted and adjusted binary logistic regressions analyzed the association of PMK at ages 14, 15, 16, and 17 with recurrent drinking after driving in 2002 (ages 18-23) and 2007 (ages 22-28). Adjusted models included age, sex, race, household income, and education. RESULTS: Mother's PMK from ages 14 to 17 was inversely associated with recurrent driving after drinking in 2002 (adjusted odds ratios [AORs]: 0.89 [p = .003, age 14], 0.93 [marginal p = .062, age 15], 0.88 [p = .0003, age 16], 0.88 [p = .0003, age 17]). By 2007, the only significant association between mother's PMK and recurrent driving after drinking was for age 16 (AOR: 0.95, p = .017). For father's PMK, significant inverse associations were only found for ages 16 and 17 with 2002 recurrent driving after drinking (AORs: 0.93, p = .025 and .88, p = .0005) and age 15 (AOR: 0.95, p = .021) with 2007 recurrent driving after drinking. DISCUSSION: Adolescent perceived PMK appears to offer protection against recurrent driving after drinking in emerging adulthood. This protective effect appears to wane as youth reach their mid-twenties.


Assuntos
Dirigir sob a Influência , Humanos , Adolescente , Feminino , Masculino , Estudos Longitudinais , Adulto Jovem , Dirigir sob a Influência/prevenção & controle , Dirigir sob a Influência/estatística & dados numéricos , Poder Familiar/psicologia , Adulto , Estudos Prospectivos , Condução de Veículo , Relações Pais-Filho , Comportamento do Adolescente/psicologia , Consumo de Bebidas Alcoólicas , Consumo de Álcool por Menores/prevenção & controle , Consumo de Álcool por Menores/estatística & dados numéricos
9.
Obesity (Silver Spring) ; 32(3): 486-493, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38053443

RESUMO

OBJECTIVE: The study's objective was to examine the percentage of patients with an initial antiobesity medication (AOM) fill who were persistent with AOM at 3, 6, and 12 months and to characterize factors associated with persistence at 12 months. METHODS: This retrospective cohort study used electronic health records from January 2015 to July 2023 in a large health system in Ohio and Florida and included adults with BMI ≥30 kg/m2 who had an initial AOM prescription filled between 2015 and 2022. RESULTS: The authors identified 1911 patients with a median baseline BMI of 38 (IQR, 34-44). Over time, 44% were persistent with AOM at 3 months, 33% at 6 months, and 19% at 12 months. Across categories of AOM, the highest 1-year persistence was in patients receiving semaglutide (40%). Semaglutide (adjusted odds ratio [AOR] = 4.26, 95% CI: 3.04-6.05) was associated with higher odds of 1-year persistence, and naltrexone-bupropion (AOR = 0.68, 95% CI: 0.46-1.00) was associated with lower odds, compared with phentermine-topiramate. Among patients who were persistent at 6 months, a 1% increase in weight loss at 6 months was associated with 6% increased odds of persistence at year 1 (AOR = 1.06, 95% CI: 1.03-1.09). CONCLUSIONS: Later-stage persistence with AOM varies considerably based on the drug and the weight loss at 6 months.


Assuntos
Fármacos Antiobesidade , Adulto , Humanos , Estudos Retrospectivos , Fármacos Antiobesidade/uso terapêutico , Redução de Peso , Ohio
10.
medRxiv ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39252910

RESUMO

Background: Guidelines recommend pharmacological venous thromboembolism (VTE) prophylaxis only for high-risk patients, but the probability of VTE considered "high-risk" is not specified. Our objective was to define an appropriate probability threshold (or range) for VTE risk stratification and corresponding prophylaxis in medical inpatients. Methods: Patients were adults admitted to any of 10 Cleveland Clinic Health System hospitals between December 2020 and August 2021 (N = 41,036). Hospital medicine physicians and internal medicine residents from included hospitals were surveyed between June and November 2023 (N = 214). We compared five approaches to determining a threshold: decision analysis, maximizing the sensitivity and specificity of a logistic regression model, deriving a probability from a point-based model, surveying physicians' understanding of VTE risk, and deriving a probability from physician behavior. For each approach, we determined the probability threshold above which a patient would be considered high-risk for VTE. We applied each threshold to the Cleveland Clinic VTE risk assessment model (CCM) and calculated the percentage of the 41,036 patients in our cohort who would be considered eligible for prophylaxis due to their high-risk status. We compared these hypothetical prophylaxis rates with physicians' observed prophylaxis rates. Results: The different approaches yielded thresholds ranging from 0.3% to 5.4%, corresponding inversely with hypothetical prophylaxis rates of 0.2% to 75%. Multiple thresholds clustered between 0.52% to 0.55%, suggesting an average hypothetical prophylaxis rate of approximately 30%, whereas physicians' observed prophylaxis rates ranged from 48% to 76%. Conclusions: Multiple approaches to determining a probability threshold for VTE prophylaxis converged to suggest an optimal threshold of approximately 0.5%. Other approaches yielded extreme thresholds that are unrealistic for clinical practice. Physicians prescribed prophylaxis much more frequently than the suggested rate of 30%, indicating opportunity to reduce unnecessary prophylaxis. To aid in these efforts, guidelines should explicitly quantify high-risk.

11.
JAMA Netw Open ; 7(9): e2433326, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39269703

RESUMO

Importance: Limited data are available on long-term weight loss achieved with semaglutide or liraglutide for type 2 diabetes (T2D) or obesity in clinical practice. Objective: To document weight loss achieved with injectable forms of semaglutide or liraglutide and identify factors associated with weight reduction of 10% or greater at 1 year. Design, Setting, and Participants: This retrospective cohort study used electronic health records from a large, integrated health system in Ohio and Florida. Participants included adults with a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of at least 30.0 who initiated treatment with semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up was completed July 28, 2023. Exposure: Injectable forms of semaglutide or liraglutide approved for T2D or obesity. Main Outcomes and Measures: Percentage weight change and categorical weight reduction of 10% or greater at 1 year. Results: A total of 3389 patients (mean [SD] age, 50.4 [12.2] years; 1835 [54.7%] female) were identified. Of these, 1341 patients received semaglutide for T2D; 1444, liraglutide for T2D; 227, liraglutide for obesity; and 377, semaglutide for obesity. Mean (SD) percentage weight change at 1 year was -5.1% (7.8%) with semaglutide vs -2.2% (6.4%) with liraglutide (P < .001); -3.2% (6.8%) for T2D as a treatment indication vs -5.9% (9.0%) for obesity (P < .001); and -5.5% (7.5%) with persistent medication coverage (ie, a cumulative gap of less than 90 days) at 1 year vs -2.8% (7.0%) with 90 to 275 medication coverage days and -1.8% (6.7%) with fewer than 90 medication coverage days (P < .001). In the multivariable model, semaglutide vs liraglutide (adjusted odds ratio [AOR], 2.19 [95% CI, 1.77-2.72]), obesity as a treatment indication vs T2D (AOR, 2.46 [95% CI, 1.83-3.30]), persistent medication coverage vs 90 medication coverage days (AOR, 3.36 [95% CI, 2.52-4.54]) or 90 to 275 medication coverage days within the first year (AOR, 1.50 [95% CI, 1.10-2.06]), high dosage of the medication vs low (AOR, 1.58 [95% CI, 1.11-2.25]), and female sex (AOR, 1.57 [95% CI, 1.27-1.94]) were associated with achieving a 10% or greater weight reduction at year 1. Conclusions and Relevance: In this retrospective cohort study of 3389 patients with obesity, weight reduction at 1 year was associated with the medication's active agent, its dosage, treatment indication, persistent medication coverage, and patient sex. Future research should focus on identifying the reasons for discontinuation of medication use and interventions aimed at improving long-term persistent coverage.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Liraglutida , Obesidade , Redução de Peso , Humanos , Liraglutida/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Redução de Peso/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Ohio , Índice de Massa Corporal , Florida
12.
Ecol Lett ; 16(4): 461-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23301667

RESUMO

The Red Queen hypothesis proposes that coevolving parasites select for outcrossing in the host. Outcrossing relies on males, which often show lower immune investment due to, for example, sexual selection. Here, we demonstrate that such sex differences in immunity interfere with parasite-mediated selection for outcrossing. Two independent coevolution experiments with Caenorhabditis elegans and its microparasite Bacillus thuringiensis produced decreased yet stable frequencies of outcrossing male hosts. A subsequent systematic analysis verified that male C. elegans suffered from a direct selective disadvantage under parasite pressure (i.e. lower resistance, decreased sexual activity, increased escape behaviour), which can reduce outcrossing and thus male frequencies. At the same time, males offered an indirect selective benefit, because male-mediated outcrossing increased offspring resistance, thus favouring male persistence in the evolving populations. As sex differences in immunity are widespread, such interference of opposing selective constraints is likely of central importance during host adaptation to a coevolving parasite.


Assuntos
Bacillus thuringiensis/fisiologia , Evolução Biológica , Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiologia , Adaptação Fisiológica/genética , Animais , Feminino , Organismos Hermafroditas , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Patógeno/genética , Masculino , Seleção Genética , Autofertilização , Caracteres Sexuais
13.
Proc Natl Acad Sci U S A ; 107(16): 7359-64, 2010 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-20368449

RESUMO

The coevolution between hosts and parasites is predicted to have complex evolutionary consequences for both antagonists, often within short time periods. To date, conclusive experimental support for the predictions is available mainly for microbial host systems, but for only a few multicellular host taxa. We here introduce a model system of experimental coevolution that consists of the multicellular nematode host Caenorhabditis elegans and the microbial parasite Bacillus thuringiensis. We demonstrate that 48 host generations of experimental coevolution under controlled laboratory conditions led to multiple changes in both parasite and host. These changes included increases in the traits of direct relevance to the interaction such as parasite virulence (i.e., host killing rate) and host resistance (i.e., the ability to survive pathogens). Importantly, our results provide evidence of reciprocal effects for several other central predictions of the coevolutionary dynamics, including (i) possible adaptation costs (i.e., reductions in traits related to the reproductive rate, measured in the absence of the antagonist), (ii) rapid genetic changes, and (iii) an overall increase in genetic diversity across time. Possible underlying mechanisms for the genetic effects were found to include increased rates of genetic exchange in the parasite and elevated mutation rates in the host. Taken together, our data provide comprehensive experimental evidence of the consequences of host-parasite coevolution, and thus emphasize the pace and complexity of reciprocal adaptations associated with these antagonistic interactions.


Assuntos
Bacillus thuringiensis/metabolismo , Caenorhabditis elegans/microbiologia , Interações Hospedeiro-Parasita , Animais , Evolução Biológica , Variação Genética , Genótipo , Repetições de Microssatélites , Modelos Biológicos , Modelos Genéticos , Parasitos , Fenótipo , Seleção Genética
14.
Trials ; 24(1): 595, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37716990

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients. METHODS: We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay. DISCUSSION: Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05568654 . Registered on October 4, 2022.


Assuntos
Anti-Infecciosos , Clostridioides difficile , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Pneumonia , Adulto , Humanos , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pacientes Internados , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
PLoS One ; 18(2): e0281660, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36758043

RESUMO

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents' understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children's antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks' antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children's antibiotics.


Assuntos
Infecções Respiratórias , Humanos , Criança , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/uso terapêutico , Pacientes Ambulatoriais , Escolaridade , Pais
16.
Biol Lett ; 8(2): 234-6, 2012 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-21880622

RESUMO

Immune responses, either constitutive or induced, are costly. An alternative defence strategy may be based on behavioural responses. For example, avoidance behaviour reduces contact with pathogens and thus the risk of infection as well as the requirement of immune system activation. Similarly, if pathogens are taken up orally, preferential feeding of pathogen-free food may be advantageous. Behavioural defences have been found in many animals, including the nematode Caenorhabditis elegans. We here tested nematodes from a laboratory based evolution experiment which had either coevolved with their microparasite Bacillus thuringiensis (BT) or evolved under control conditions. After 48 generations, coevolved populations were more sensitive to food conditions: in comparison with the controls, they reduced feeding activity in the presence of pathogenic BT strains while at the same time increasing it in the presence of non-pathogenic strains. We conclude that host-parasite coevolution can drive changes in the behavioural responsiveness to bacterial microbes, potentially leading to an increased defence against pathogens.


Assuntos
Bacillus thuringiensis/fisiologia , Evolução Biológica , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Animais , Caenorhabditis elegans/genética , Comportamento Alimentar , Genótipo , Seleção Genética
17.
Drug Alcohol Depend ; 232: 109328, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101815

RESUMO

BACKGROUND: To characterize emerging adults' drinking trajectories and their prospective association with later behavior, health, education, and work outcomes in later young adulthood. METHODS: This study used a selected cohort (N = 1622) from rounds 3-10 (aged 18-25), 11 (aged 26), 14 (aged 29), and 17 (aged 34) of the US National Longitudinal Survey of Youth 1997. Latent class growth modeling was used to identify trajectories of drinking (days ≥1 drink in the last 30 days) during emerging adulthood (aged 18-25) using data from rounds 3-10. Multinomial and linear regressions compared identified trajectory classes to outcomes measured 1, 4, and 9 years later. Covariates included sex, race, and urbanicity. RESULTS: Six drinking trajectories were identified: Abstainers (28.42%), Moderate Increasers (24.78%), Light Experimenters (11.96%), Heavy Experimenters (9.86%), Escalators (17.26%), and Heavy Users (7.71%). Compared to abstainers, emerging adults in other classes had significantly (p < .05 to.001) higher odds of binge drinking, smoking, and marijuana use at later rounds. Compared to abstainers, escalators had significantly higher education and income later. No significant difference in physical or mental health was found. CONCLUSION: Drinking behaviors formed during emerging adulthood continue into later lifetime periods in adulthood. The experimenters shifted their drinking behaviors to greater smoking and marijuana use, while heavy users supplemented their drinking behavior. Interventions in emerging adulthood (particularly ages 19-21), the period when individuals are becoming more independent but malleable, may mitigate adverse effects of alcohol overuse and improve later life behaviors and career outcomes.


Assuntos
Uso da Maconha , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Escolaridade , Comportamentos Relacionados com a Saúde , Humanos , Estudos Longitudinais , Fumar , Adulto Jovem
18.
J Autism Dev Disord ; 52(10): 4321-4336, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34637019

RESUMO

Interest continues to be high in technology-based interventions for individuals with autism spectrum disorder (ASD). Understanding the preferences and challenges of technology use among individuals with ASD can inform the design of such interventions. Through 18 interviews with parents, we used an iterative inductive-deductive approach to qualitative analysis and explored uses of technology for social skills development among adolescents with ASD. Our findings include parents' observations about their adolescent's preferences in types of technology devices and digital content, as well as both positive and negative effects of technology use on mood and behavior. Parents highlighted several avenues of technological preferences and risks that may inform intervention design, enhance user engagement, and capitalize on users' strengths while buttressing areas for growth.


Assuntos
Transtorno do Espectro Autista , Adolescente , Transtorno do Espectro Autista/terapia , Humanos , Pais , Habilidades Sociais , Tecnologia
19.
Proc Biol Sci ; 278(1719): 2832-9, 2011 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-21307053

RESUMO

Coevolving hosts and parasites can adapt to their local antagonist. In studies on natural populations, the observation of local adaptation patterns is thus often taken as indirect evidence for coevolution. Based on this approach, coevolution was previously inferred from an overall pattern of either parasite or host local adaptation. Many studies, however, failed to detect such a pattern. One explanation is that the studied system was not subject to coevolution. Alternatively, coevolution occurred, but remained undetected because it took different routes in different populations. In some populations, it is the host that is locally adapted, whereas in others it is the parasite, leading to the absence of an overall local adaptation pattern. Here, we test for overall as well as population-specific patterns of local adaptation using experimentally coevolved populations of the nematode Caenorhabditis elegans and its bacterial microparasite Bacillus thuringiensis. Furthermore, we assessed the importance of random interaction effects using control populations that evolved in the absence of the respective antagonist. Our results demonstrate that experimental coevolution produces distinct local adaptation patterns in different replicate populations, including host, parasite or absence of local adaptation. Our study thus provides experimental evidence of the predictions of the geographical mosaic theory of coevolution, i.e. that the interaction between parasite and host varies across populations.


Assuntos
Adaptação Fisiológica , Bacillus thuringiensis/fisiologia , Evolução Biológica , Caenorhabditis elegans/parasitologia , Interações Hospedeiro-Parasita/fisiologia , Animais , Caenorhabditis elegans/fisiologia
20.
Womens Health Issues ; 31(5): 455-461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34090780

RESUMO

PURPOSE: For reproductive-age women, medications for opioid use disorder (OUD) decrease risk of overdose death and improve outcomes but are underutilized. Our objective was to provide a qualitative description of reproductive-age women's experiences of seeking an appointment for medications for OUD. METHODS: Trained female callers placed telephone calls to a representative sample of publicly listed opioid treatment clinics and buprenorphine providers in Florida, Kentucky, Massachusetts, Michigan, Missouri, North Carolina, Tennessee, Virginia, Washington, and West Virginia to obtain appointments to receive medication for OUD. Callers were randomly assigned to be pregnant or non-pregnant and have private or Medicaid-based insurance to assess differences in the experiences of access by these characteristics. The callers placed 28,651 uniquely randomized calls, 10,117 to buprenorphine-waivered prescribers and 754 to opioid treatment programs. Open-ended, qualitative data were obtained from the callers about the access experiences and were analyzed using a qualitative, iterative inductive-deductive approach. From all 28,651 total calls, there were 17,970 unique free-text comments to the question "Please give an objective play-by-play of the description of what happened in this conversation." FINDINGS: Analysis demonstrated a common path to obtaining an appointment. Callers frequently experienced long hold times, multiple transfers, and difficult interactions. Clinic receptionists were often mentioned as facilitating or obstructing access. Pregnant callers and those with Medicaid noted more barriers. Obtaining an appointment was commonly difficult even for these persistent, trained callers. CONCLUSIONS: Interventions are needed to improve the experiences of reproductive-age women as they enter care for OUD, especially for pregnant women and those with Medicaid coverage.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Agendamento de Consultas , Buprenorfina/uso terapêutico , Feminino , Humanos , Medicaid , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Gravidez , Estados Unidos
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