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BACKGROUND: Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT). METHODS: We performed a retrospective cohort study to measure the independent association between intensity of antibiotic therapy, as measured by the antibiotic spectrum index (ASI), and hospital-associated CDI (HA-CDI) at a large academic medical center between January 2018 and March 2020. We constructed a marginal Poisson regression model to generate adjusted relative risks for a unit increase in ASI per antibiotic day. RESULTS: We included 35,457 inpatient encounters in our cohort. Sixty-eight percent of patients received at least one antibiotic. We identified 128 HA-CDI cases, which corresponds to an incidence rate of 4.1 cases per 10,000 patient-days. After adjusting for known confounders, each additional unit increase in ASI per antibiotic day is associated with 1.09 times the risk of HA-CDI (Relative Risk = 1.09, 95% Confidence Interval: 1.06 to 1.13). CONCLUSIONS: ASI was strongly associated with HA-CDI and could be a useful tool in evaluating the impact of antibiotic stewardship on HA-CDI rates, providing more granular information than the more commonly used days of therapy.
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Background: Clinical research focused on the burden and impact of Clostridioides difficile infection (CDI) often relies upon accurate identification of cases using existing health record data. Use of diagnosis codes alone can lead to misclassification of cases. Our goal was to develop and validate a multi-component algorithm to identify hospital-associated CDI (HA-CDI) cases using electronic health record (EHR) data. Methods: We performed a validation study using a random sample of adult inpatients at a large academic hospital setting in Portland, Oregon from January 2018 to March 2020. We excluded patients with CDI on admission and those with short lengths of stay (< 4 days). We tested a multi-component algorithm to identify HA-CDI; case patients were required to have received an inpatient course of metronidazole, oral vancomycin, or fidaxomicin and have at least one of the following: a positive C. difficile laboratory test or the International Classification of Diseases, Tenth Revision (ICD-10) code for non-recurrent CDI. For a random sample of 80 algorithm-identified HA-CDI cases and 80 non-cases, we performed manual EHR review to identify gold standard of HA-CDI diagnosis. We then calculated overall percent accuracy, sensitivity, specificity, and positive and negative predictive value for the algorithm overall and for the individual components. Results: Our case definition algorithm identified HA-CDI cases with 94% accuracy (95% Confidence Interval (CI): 88% to 97%). We achieved 100% sensitivity (94% to 100%), 89% specificity (81% to 95%), 88% positive predictive value (78% to 94%), and 100% negative predictive value (95% to 100%). Requiring a positive C. difficile test as our gold standard further improved diagnostic performance (97% accuracy [93% to 99%], 93% PPV [85% to 98%]). Conclusions: Our algorithm accurately detected true HA-CDI cases from EHR data in our patient population. A multi-component algorithm performs better than any isolated component. Requiring a positive laboratory test for C. difficile strengthens diagnostic performance even further. Accurate detection could have important implications for CDI tracking and research.
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Objective: To describe the First Responder Shock Trial (FIRST), which aims to determine whether equipping frequently responding, smartphone-activated (GoodSAM) first responders with an ultraportable AED can increase 30-day survival rates in OHCA. Methods: The FIRST trial is an investigator-initiated, bi-national (Victoria, Australia and New Zealand), registry-nested cluster-randomised controlled trial where the unit of randomisation is the smartphone-activated (GoodSAM) first responder. High-frequency GoodSAM responders are randomised 1:1 to receive an ultraportable, single-use AED or standard alert procedures using the GoodSAM app.The primary outcome is survival to 30 days. The secondary outcome measures (shockable rhythm, return of spontaneous circulation, event survival, and time to first shock delivery) are routinely collected by OHCA registries in both regions. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (Registration: ACTRN12622000448741) on 22 March 2022. Results: The trial started in November 2022 and the last patient is expected to be enrolled in November 2024. We aim to detect a 7% increase in the proportion of 30-day survivors, from 9% in patients attended by control responders to 16% in patients attended by responders randomised to the ultraportable AED intervention arm. With 80% power, an alpha of 0.05, a cluster size of 1.5 and a coefficient of variation for cluster sizes of 1, the sample size required to detect this difference is 714 (357 per arm). Conclusion: The FIRST study will increase our understanding of the potential role of portable AED use by smartphone-activated community responders and their impact on survival outcomes.
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Aim: To understand the fear and willingness to respond of smartphone activated first responders during the COVID-19 pandemic. Methods: We invited smartphone activated first responders registered with the GoodSAM application in Victoria, Australia to take part in an online survey in November 2020. We assessed willingness to respond to an alert and provide CPR during the pandemic and administered the Fear of COVID-19 Scale questionnaire. Regression analysis was conducted to investigate associations between occupation, clinical training, and years of clinical experience with willingness to respond and fear of COVID-19. Results: The survey response rate was 5.1%. Responders (n = 348) had a median age (interquartile range) of 46 years (33-55). Most (67%) were aged 30-59 years and 43% were female. Responders spanned several occupations including paramedics (12.6%), registered nurses (14.7%), and non-clinical individuals (21.8%). Most (92%) reported they would feel comfortable responding to a GoodSAM alert during the pandemic. Almost all (>95%) reported they would provide CPR. About 20% reported being afraid of COVID-19 but only 3.2% reported they had a high-level of fear of COVID-19. The odds of paramedics being willing to respond to an alert was reduced by 73% during the pandemic (OR 0.27, 95% CI 0.11 to 0.69). No other associations were found with willingness or fear of COVID-19. Conclusion: Although willingness was high and fear of COVID-19 was low, some smartphone activated first responders were less willing to respond to an alert during the pandemic. These findings may inform future pandemic planning and decision-making around pausing first-responder programs.
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As the smallest mammal with a gyrencephalic cerebral cortex, ferrets are becoming increasingly important animal models to study neurological disorders. In order for them to be optimally used, typical behavioral measurements are highly desirable. To ascertain a baseline level of behavior, we conducted a battery of tests assessing motor, social, memory, headache, and aspects of depressive-like behavior. Adult male ferrets participated in open field, beam walk, sucrose preference, eye contact, light/dark box, socialization, and novel object recognition tests. The animals were assessed in three cohorts, which differed in age, with the youngest group being approximately 1 year younger than the oldest. Small, but significant, differences occurred between the youngest cohort and the older groups in several areas, suggesting that age may be an important factor when evaluating ferret behavior. Ferrets showed a high level of sociability in the eye contact tests and with novel animal preference. These experiments represent an important baseline of expected normative results that can provide a reference for normal ferret behavior and expected variability. The data reported here may serve as a reference for future intervention studies using the ferret. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Escala de Avaliação Comportamental , Furões , Animais , Córtex Cerebral , Humanos , MasculinoRESUMO
BACKGROUND: Responder smartphone apps use global positioning data to enable emergency medical services to alert volunteer responders of nearby potential out-of-hospital cardiac arrests (OHCA). AIM: To assess volunteer availability, interventions provided and frequency of probable post traumatic stress disorder (PTSD) experienced by responders receiving a smartphone alert. METHODS: A web-based survey was emailed to alerted responders at week-two post-alert and a PTSD screening survey at week-six, in Victoria, Australia (1/08/2019-8/11/2020), and in New Zealand (18/02/2020-28/10/2020). RESULTS: We received 1,985 responses to the week-two survey and 1,443 responses to the week-six survey. Of the 1,985 responders, 1,744 (87.9%) had completed cardiopulmonary resuscitation (CPR) training in the last twelve months, and 1,514 (76.3%) had performed CPR at least once. The alert was seen by 1,501 (75.6%) responders, 749 (37.7%) accepted the alert, 538 (27.1%) arrived on scene, and 283 (14.3%) provided care to the patient. In the multivariable analysis, CPR training within twelve months was associated with increased odds of responders accepting alerts (AOR 1.41, 95%CI: 1.02-1.96; p=0.040). Responders who had performed CPR before, were more than twice as likely to provide patient care compared to responders who had not (AOR 2.54, 95%CI: 1.56-4.12; p<0.001). One responder screened positive for probable PTSD. CONCLUSION: Acceptance rates in Australia and New Zealand were consistent with other smartphone apps. Responder recruitment should be targeted at those with medical backgrounds who have prior CPR experience, as they are more likely to provide care. The very low risk of PTSD is reassuring information when recruiting volunteers.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Transtornos de Estresse Pós-Traumáticos , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Smartphone , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Vitória , VoluntáriosRESUMO
The '2021 AAFP Feline Senior Care Guidelines' are authored by a Task Force of experts in feline clinical medicine and serve as an update and extension of those published in 2009. They emphasize the individual patient evaluation and the process of aging, with references to other feline practice guidelines for a more complete discussion of specific diseases. Focusing on each cat encourages and empowers the owner to become a part of the cat's care every step of the way. A comprehensive discussion during the physical examination and history taking allows for tailoring the approach to both the cat and the family involved in the care. Videos and analysis of serial historical measurements are brought into the assessment of each patient. These Guidelines introduce the emerging concept of frailty, with a description and methods of its incorporation into the senior cat assessment. Minimum database diagnostics are discussed, along with recommendations for additional investigative considerations. For example, blood pressure assessment is included as a minimum diagnostic procedure in both apparently healthy and ill cats. Cats age at a much faster rate than humans, so practical timelines for testing frequency are included and suggest an increased frequency of diagnostics with advancing age. The importance of nutrition, as well as senior cat nutritional needs and deficiencies, is considered. Pain is highlighted as its own syndrome, with an emphasis on consideration in every senior cat. The Task Force discusses anesthesia, along with strategies to allow aging cats to be safely anesthetized well into their senior years. The medical concept of quality of life is addressed with the latest information available in veterinary medicine. This includes end of life considerations like palliative and hospice care, as well as recommendations on the establishment of 'budgets of care', which greatly influence what can be done for the individual cat. Acknowledgement is given that each cat owner will be different in this regard; and establishing what is reasonable and practical for the individual owner is important. A discussion on euthanasia offers some recommendations to help the owner make a decision that reflects the best interests of the individual cat.
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Anestesia , Doenças do Gato , Anestesia/veterinária , Animais , Doenças do Gato/diagnóstico , Doenças do Gato/terapia , Gatos , Humanos , Dor/veterinária , Cuidados Paliativos , Exame Físico , Qualidade de VidaRESUMO
PURPOSE: Our purpose was to survey nationwide radiation oncology practices on their participation in, burden of, and satisfaction with the Medicare Access and Children's Health Insurance Program Reauthorization Act of 2015 (MACRA) payment programs. METHODS AND MATERIALS: All radiation oncology practices accredited by a national specialty organization were invited to participate in a voluntary online survey from December 2018 to January 2019. Questions focused on participation in the Merit-based Incentive Payment System (MIPS) in 2017 and 2018, as by the time of this survey, radiation oncology did not yet have a specialty-specific advanced Alternative Payment Model. RESULTS: Of n = 705 solicited practices, n = 199 completed the survey for an overall response rate of 28.2%. Practices varied significantly in their duration of participation in MACRA programs, means of data submission, and reported improvement activities under MIPS. Forty-nine percent of respondents described being either somewhat or extremely dissatisfied with the ease of submitting measures and data in 2018. The estimated cost to the practices of compliance with MACRA was queried in bins; of users able to estimate the cost of compliance for 2018, the median reported bin was $10,001 to $20,000 (range, less than $1000-100,000 or more). CONCLUSIONS: The participation style in MACRA among radiation oncology practices varied substantially in the years 2017 and 2018. The Center for Medicare & Medicaid Services gave no precise estimates on the cost of compliance for MIPS, but estimated a $3019.47 cost of compliance with the mandated Radiation Oncology Alternative Payment Model in the 2020 Final Rule for selected practices. In this survey, respondents commonly reported the cost of compliance with MACRA significantly exceeded this estimate.
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Medicare Access and CHIP Reauthorization Act of 2015 , Radioterapia (Especialidade)/estatística & dados numéricos , Reembolso de Incentivo/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Atitude do Pessoal de Saúde , Centers for Medicare and Medicaid Services, U.S. , Registros Eletrônicos de Saúde , Humanos , Medicare Access and CHIP Reauthorization Act of 2015/economia , Medicare Access and CHIP Reauthorization Act of 2015/estatística & dados numéricos , Radioterapia (Especialidade)/economia , Reembolso de Incentivo/legislação & jurisprudência , Estados UnidosRESUMO
OBJECTIVES: To identify the frequency with which antibiotics are prescribed in the absence of a documented indication in the ambulatory care setting, to quantify the potential effect on assessments of appropriateness of antibiotics, and to understand patient, provider, and visit level characteristics associated with antibiotic prescribing without a documented indication. DESIGN: Cross sectional study. SETTING: 2015 National Ambulatory Medical Care Survey. PARTICIPANTS: 28 332 sample visits representing 990.9 million ambulatory care visits nationwide. MAIN OUTCOME MEASURES: Overall antibiotic prescribing and whether each antibiotic prescription was accompanied by appropriate, inappropriate, or no documented indication as identified through ICD-9-CM (international classification of diseases, 9th revision, clinical modification) codes. Survey weighted multivariable logistic regression was used to evaluate potential risk factors for receipt of an antibiotic prescription without a documented indication. RESULTS: Antibiotics were prescribed during 13.2% (95% confidence interval 11.6% to 13.7%) of the estimated 990.8 million ambulatory care visits in 2015. According to the criteria, 57% (52% to 62%) of the 130.5 million prescriptions were for appropriate indications, 25% (21% to 29%) were inappropriate, and 18% (15% to 22%) had no documented indication. This corresponds to an estimated 24 million prescriptions without a documented indication. Being an adult male, spending more time with the provider, and seeing a non-primary care specialist were significantly positively associated with antibiotic prescribing without an indication. Sulfonamides and urinary anti-infective agents were the antibiotic classes most likely to be prescribed without documentation. CONCLUSIONS: This nationally representative study of ambulatory visits identified a large number of prescriptions for antibiotics without a documented indication. Antibiotic prescribing in the absence of a documented indication may severely bias national estimates of appropriate antibiotic use in this setting. This study identified a wide range of factors associated with antibiotic prescribing without a documented indication, which may be useful in directing initiatives aimed at supporting better documentation.
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Instituições de Assistência Ambulatorial , Antibacterianos/farmacologia , Uso de Medicamentos/normas , Prescrição Inadequada/estatística & dados numéricos , Padrões de Prática Médica , Estudos Transversais , Humanos , Fatores de Risco , Estados UnidosRESUMO
AIM: The overarching purpose of the 2019 AAFP Feline Zoonoses Guidelines (hereafter referred to as the 'Guidelines') is to provide accurate information about feline zoonotic diseases to owners, physicians and veterinarians to allow logical decisions to be made concerning cat ownership. SCOPE AND ACCESSIBILITY: The Panelists are physicians and veterinarians who worked closely together in an attempt to make these Guidelines a document that can be used to support the International One Health movement. This version of the Guidelines builds upon the first feline zoonosis panel report, published in 2003 ( catvets.com/guidelines ), and provides an updated reference list and recommendations. Each of the recommendations received full support from every Panelist. Primary recommendations are highlighted in a series of 'Panelists' advice' boxes.
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Doenças do Gato , Guias como Assunto , Zoonoses , Animais , Doenças do Gato/diagnóstico , Doenças do Gato/etiologia , Doenças do Gato/transmissão , Gatos , Humanos , Propriedade , Médicos , Médicos Veterinários , Zoonoses/diagnóstico , Zoonoses/etiologia , Zoonoses/transmissãoRESUMO
BACKGROUND: The continued rise in fatalities from opioid analgesics despite a steady decline in the number of individual prescriptions directing ≥ 90 morphine milligram equivalents (MME)/day may be explained by patient exposures to redundant prescriptions from multiple prescribers. OBJECTIVES: We evaluated prescribers' specialty and social network characteristics associated with high-risk opioid exposures resulting from single-prescriber high-daily dose prescriptions or multi-prescriber discoordination. DESIGN: Retrospective cohort study. PARTICIPANTS: A cohort of prescribers with opioid analgesic prescription claims for non-cancer chronic opioid users in an Illinois Medicaid managed care program in 2015-2016. MAIN MEASURES: Per prescriber rates of single-prescriber high-daily-dose prescriptions or multi-prescriber discoordination. KEY RESULTS: For 2280 beneficiaries, 36,798 opioid prescription claims were submitted by 3532 prescribers. Compared to 3% of prescriptions (involving 6% of prescribers and 7% of beneficiaries) that directed ≥ 90 MME/day, discoordination accounted for a greater share of high-risk exposures-13% of prescriptions (involving 23% of prescribers and 24% of beneficiaries). The following specialties were at highest risk of discoordinated prescribing compared to internal medicine: dental (incident rate ratio (95% confidence interval) 5.9 (4.6, 7.5)), emergency medicine (4.7 (3.8, 5.8)), and surgical subspecialties (4.2 (3.0, 5.8)). Social network analysis identified 2 small interconnected prescriber communities of high-volume pain management specialists, and 3 sparsely connected groups of predominantly low-volume primary care or emergency medicine clinicians. Using multivariate models, we found that the sparsely connected sociometric positions were a risk factor for high-risk exposures. CONCLUSION: Low-volume prescribers in the social network's periphery were at greater risk of intended or discoordinated prescribing than interconnected high-volume prescribers. Interventions addressing discoordination among low-volume opioid prescribers in non-integrated practices should be a priority. Demands for enhanced functionality and integration of Prescription Drug Monitoring Programs or referrals to specialized multidisciplinary pain management centers are potential policy implications.
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Analgésicos Opioides/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , Medicina de Emergência , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Programas de Monitoramento de Prescrição de Medicamentos/estatística & dados numéricos , Atenção Primária à Saúde , Estudos Retrospectivos , Rede SocialRESUMO
BACKGROUND & AIMS: Pancreatitis is a major cause of morbidity and mortality and is a risk factor for pancreatic tumorigenesis. Upon tissue damage, an inflammatory response, made up largely of macrophages, provides multiple growth factors that promote repair. Here, we examine the molecular pathways initiated by macrophages to promote pancreas recovery from pancreatitis. METHODS: To induce organ damage, mice were subjected to cerulein-induced experimental pancreatitis and analyzed at various times of recovery. CD11b-DTR mice were used to deplete myeloid cells. Hbegff/f;LysM-Cre mice were used to ablate myeloid cell-derived heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF). To ablate EGFR specifically during recovery, pancreatitis was induced in Egfrf/f;Ptf1aFlpO/+;FSF-Rosa26CAG-CreERT2 mice followed by tamoxifen treatment. RESULTS: Macrophages infiltrating the pancreas in experimental pancreatitis make high levels of HB-EGF. Both depletion of myeloid cells and ablation of myeloid cell HB-EGF delayed recovery from experimental pancreatitis, resulting from a decrease in cell proliferation and an increase in apoptosis. Mechanistically, ablation of myeloid cell HB-EGF impaired epithelial cell DNA repair, ultimately leading to cell death. Soluble HB-EGF induced EGFR nuclear translocation and methylation of histone H4, facilitating resolution of DNA damage in pancreatic acinar cells in vitro. Consistent with its role as the primary receptor of HB-EGF, in vivo ablation of EGFR from pancreatic epithelium during recovery from pancreatitis resulted in accumulation of DNA damage. CONCLUSIONS: By using novel conditional knockout mouse models, we determined that HB-EGF derived exclusively from myeloid cells induces epithelial cell proliferation and EGFR-dependent DNA repair, facilitating pancreas healing after injury.
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Reparo do DNA , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Células Mieloides/metabolismo , Pâncreas/fisiologia , Pancreatite/fisiopatologia , Regeneração , Animais , DNA/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/farmacologia , Camundongos , Camundongos KnockoutRESUMO
PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.
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Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Medicina Baseada em Evidências , Humanos , Masculino , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Timely identification of patients likely to harbor carbapenem-resistant Enterobacteriaceae (CRE) can help health care facilities provide effective infection control and treatment. We evaluated whether a model utilizing prior health care information from a state hospital discharge database could predict a patient's probability of CRE colonization at the time of hospital admission. METHODS: We performed a case-control study using the Illinois hospital discharge database. From a 2014-2015 patient cohort, we defined cases as index adult patient hospital encounters with a positive CRE culture collected within the first 3 days of hospitalization, as reported to the Illinois XDRO registry; controls were all patient admissions from the same hospital and month. We split the data into training (~60%) and validation (~40%) sets and developed a logistic regression model to estimate coefficients for predictors of interest. RESULTS: We identified 486 index cases and 340 005 controls. Independent risk factors for CRE at the time of admission were age, number of short-term acute care hospital (STACH) hospitalizations in the prior 365 days, mean STACH length of stay, number of long-term acute care hospital (LTACH) hospitalizations in the prior 365 days, mean LTACH length of stay, current admission to LTACH, and prior hospital admission with an infection diagnosis code. When applying the model to the validation data set, the area under the receiver operating characteristic curve was 0.84. CONCLUSIONS: A prediction model utilizing prior health care exposure information could discriminate patients who were likely to harbor CRE at the time of hospital admission.
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PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.
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Medicina Baseada em Evidências/normas , Guias de Prática Clínica como Assunto/normas , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Radioterapia (Especialidade)/normas , Radioterapia Conformacional/métodos , Consenso , Seguimentos , Humanos , Masculino , PrognósticoRESUMO
Approximately 20,000 US veterans receive radiation oncology services at a Veterans Healthcare Administration (VHA) medical facility each year. They currently have access to advanced technologies, which include image-guided intensity-modulated radiotherapy, stereotactic radiosurgery, and stereotactic body radiation therapy. Although this provides access to cancer therapies that are modern, safe, and efficient, the technical complexities of these treatments and clinical decision making that goes into the patient selection and prescriptions demand quality assurances at each VHA practice. To meet the challenges of this need, the VHA established a partnership in 2008 with the ACR's Radiation Oncology Practice Accreditation Program (ACR-ROPA). This report summarizes the experience of this ongoing partnership and demonstrates the combined impact of the VHA's mandate for ACR-ROPA accreditation and internal monitoring of all identified corrective actions at each of its radiation oncology practices.
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Acreditação , Melhoria de Qualidade , Radioterapia (Especialidade)/normas , Saúde dos Veteranos/normas , Humanos , Conselhos de Especialidade Profissional , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans AffairsRESUMO
OBJECTIVETo evaluate probiotics for the primary prevention of Clostridium difficile infection (CDI) among hospital inpatients.DESIGNA before-and-after quality improvement intervention comparing 12-month baseline and intervention periods.SETTINGA 694-bed teaching hospital.INTERVENTIONWe administered a multispecies probiotic comprising L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2) to eligible antibiotic recipients within 12 hours of initial antibiotic receipt through 5 days after final dose. We excluded (1) all patients on neonatal, pediatric and oncology wards; (2) all individuals receiving perioperative prophylactic antibiotic recipients; (3) all those restricted from oral intake; and (4) those with pancreatitis, leukopenia, or posttransplant. We defined CDI by symptoms plus C. difficile toxin detection by polymerase chain reaction. Our primary outcome was hospital-onset CDI incidence on eligible hospital units, analyzed using segmented regression.RESULTSThe study included 251 CDI episodes among 360,016 patient days during the baseline and intervention periods, and the incidence rate was 7.0 per 10,000 patient days. The incidence rate was similar during baseline and intervention periods (6.9 vs 7.0 per 10,000 patient days; P=.95). However, compared to the first 6 months of the intervention, we detected a significant decrease in CDI during the final 6 months (incidence rate ratio, 0.6; 95% confidence interval, 0.4-0.9; P=.009). Testing intensity remained stable between the baseline and intervention periods: 19% versus 20% of stools tested were C. difficile positive by PCR, respectively. From medical record reviews, only 26% of eligible patients received a probiotic per the protocol.CONCLUSIONSDespite poor adherence to the protocol, there was a reduction in the incidence of CDI during the intervention, which was delayed ~6 months after introducing probiotic for primary prevention.Infect Control Hosp Epidemiol 2018;765-770.
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Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Prevenção Primária/métodos , Probióticos/uso terapêutico , Estudos de Casos e Controles , Chicago/epidemiologia , Clostridioides difficile , Infecção Hospitalar/microbiologia , Hospitais de Ensino , Humanos , Melhoria de Qualidade , Centros de Atenção TerciáriaRESUMO
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing ß-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult ß-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. METHODS: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. RESULTS: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult ß-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. CONCLUSIONS: Our data provide stage-specific target genes of PDX1 during in vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a ß-cell developmental program.