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The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to review the validity of this broad term in an era of swiftly advancing science and targeted therapeutics. A Delphi approach was used to define and interrogate some of the key issues related to the atypical hemolytic uremic syndrome nomenclature.
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Síndrome Hemolítico-Urêmica Atípica , Técnica Delphi , Terminologia como Assunto , Humanos , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Consenso , Nefrologia/normasRESUMO
About 37 million people in the United States have chronic kidney disease, a disease that encompasses diseases of multiple causes. About 10% or more of kidney diseases in adults and about 70% of selected chronic kidney diseases in children are expected to be explained by genetic causes. Despite the advances in genetic testing and an increasing understanding of the genetic bases of certain kidney diseases, genetic testing in nephrology lags behind other medical fields. More understanding of the benefits and logistics of genetic testing is needed to advance the implementation of genetic testing in chronic kidney diseases. Accordingly, the National Kidney Foundation convened a Working Group of experts with diverse expertise in genetics, nephrology, and allied fields to develop recommendations for genetic testing for monogenic disorders and to identify genetic risk factors for oligogenic and polygenic causes of kidney diseases. Algorithms for clinical decision making on genetic testing and a road map for advancing genetic testing in kidney diseases were generated. An important aspect of this initiative was the use of a modified Delphi process to reach group consensus on the recommendations. The recommendations and resources described herein provide support to nephrologists and allied health professionals to advance the use of genetic testing for diagnosis and screening of kidney diseases.
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Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) has rarely included the perspectives of providers from a variety of health care disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and a half-day workshop that convened a multidisciplinary group of physicians, allied health care professionals, and pediatric patients with CKD and their parents, with the goal of developing key clinical recommendations regarding best practices for the clinical management of pediatric patients living with CKD. The key clinical recommendations pertained to 5 broad topics: addressing the needs of patients and parents/caregivers; modifying the progression of CKD; clinical management of CKD-mineral and bone disorder and growth retardation; clinical management of anemia, cardiovascular disease, and hypertension; and transition and transfer of pediatric patients to adult nephrology care. This report describes the recommendations generated by the participants who attended the workshop.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Nefrologia , Médicos , Insuficiência Renal Crônica , Adulto , Humanos , Criança , Insuficiência Renal Crônica/terapia , RimRESUMO
Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents myriad questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anticomplement therapy trials either planned or under way, the National Kidney Foundation facilitated an all-virtual scientific workshop entitled "Improving Clinical Trials for Anti-Complement Therapies in Complement-Mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anticomplement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, participant risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.
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Proteínas Inativadoras do Complemento , Nefropatias , Proteínas Inativadoras do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Humanos , RimRESUMO
A large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. We generated a fully human antibody (MAA868) that binds the catalytic domain of both FXI (zymogen) and activated FXI. Our structural studies show that MAA868 traps FXI and activated FXI in an inactive, zymogen-like conformation, explaining its equally high binding affinity for both forms of the enzyme. This binding mode allows the enzyme to be neutralized before entering the coagulation process, revealing a particularly attractive anticoagulant profile of the antibody. MAA868 exhibited favorable anticoagulant activity in mice with a dose-dependent protection from carotid occlusion in a ferric chloride-induced thrombosis model. MAA868 also caused robust and sustained anticoagulant activity in cynomolgus monkeys as assessed by activated partial thromboplastin time without any evidence of bleeding. Based on these preclinical findings, we conducted a first-in-human study in healthy subjects and showed that single subcutaneous doses of MAA868 were safe and well tolerated. MAA868 resulted in dose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time and FXI suppression for up to 4 weeks or longer, supporting further clinical investigation as a potential once-monthly subcutaneous anticoagulant therapy.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Fator XI/antagonistas & inibidores , Trombose/tratamento farmacológico , Adolescente , Adulto , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Anticoagulantes/farmacologia , Feminino , Humanos , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Macaca fascicularis , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Trombose/sangue , Adulto JovemRESUMO
Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and-most critically-patients with Alport syndrome. Recommendations were established for preclinical researchers, the use and selection of biomarkers, standards of care, clinical trial designs, trial eligibility criteria and outcomes, pediatric trial considerations, and considerations for patient engagement, recruitment, and treatment. This paper outlines their recommendations.
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Transplante de Rim , Nefrite Hereditária , Biomarcadores , Criança , Humanos , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/tratamento farmacológico , Estudos ProspectivosRESUMO
OBJECTIVE: This study determined whether angiotensinogen (AGT) has angiotensin II-independent effects using multiple genetic and pharmacological manipulations. APPROACH AND RESULTS: All study mice were in low-density lipoprotein receptor -/- background and fed a saturated fat-enriched diet. In mice with floxed alleles and a neomycin cassette in intron 2 of the AGT gene (hypoAGT mice), plasma AGT concentrations were >90% lower compared with their wild-type littermates. HypoAGT mice had lower systolic blood pressure, less atherosclerosis, and diminished body weight gain and liver steatosis. Low plasma AGT concentrations and all phenotypes were recapitulated in mice with hepatocyte-specific deficiency of AGT or pharmacological inhibition of AGT by antisense oligonucleotide administration. In contrast, inhibition of AGT cleavage by a renin inhibitor, aliskiren, failed to alter body weight gain and liver steatosis in low-density lipoprotein receptor -/- mice. In mice with established adiposity, administration of AGT antisense oligonucleotide versus aliskiren led to equivalent reductions of systolic blood pressure and atherosclerosis. AGT antisense oligonucleotide administration ceased body weight gain and further reduced body weight, whereas aliskiren did not affect body weight gain during continuous saturated fat-enriched diet feeding. Structural comparisons of AGT proteins in zebrafish, mouse, rat, and human revealed 4 highly conserved sequences within the des(angiotensin I)AGT domain. des(angiotensin I)AGT, through adeno-associated viral infection in hepatocyte-specific AGT-deficient mice, increased body weight gain and liver steatosis, but did not affect atherosclerosis. CONCLUSIONS: AGT contributes to body weight gain and liver steatosis through functions of the des(angiotensin I)AGT domain, which are independent of angiotensin II production.
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Angiotensina II/metabolismo , Angiotensinogênio/metabolismo , Aterosclerose/metabolismo , Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Hipertensão/metabolismo , Fígado/metabolismo , Amidas/farmacologia , Sequência de Aminoácidos , Angiotensinogênio/deficiência , Angiotensinogênio/genética , Animais , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Pressão Sanguínea , Sequência Conservada , Dependovirus/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Fumaratos/farmacologia , Vetores Genéticos , Genótipo , Hepatócitos/patologia , Hipertensão/genética , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Moleculares , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Fenótipo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores de LDL/deficiência , Receptores de LDL/genética , Renina/antagonistas & inibidores , Renina/metabolismo , Transdução de Sinais , Fatores de Tempo , Transdução Genética , Aumento de PesoRESUMO
Catchment urbanization perturbs the water and sediment budgets of streams, degrades stream health and function, and causes a constellation of flow, water quality, and ecological symptoms collectively known as the urban stream syndrome. Low-impact development (LID) technologies address the hydrologic symptoms of the urban stream syndrome by mimicking natural flow paths and restoring a natural water balance. Over annual time scales, the volumes of stormwater that should be infiltrated and harvested can be estimated from a catchment-scale water-balance given local climate conditions and preurban land cover. For all but the wettest regions of the world, a much larger volume of stormwater runoff should be harvested than infiltrated to maintain stream hydrology in a preurban state. Efforts to prevent or reverse hydrologic symptoms associated with the urban stream syndrome will therefore require: (1) selecting the right mix of LID technologies that provide regionally tailored ratios of stormwater harvesting and infiltration; (2) integrating these LID technologies into next-generation drainage systems; (3) maximizing potential cobenefits including water supply augmentation, flood protection, improved water quality, and urban amenities; and (4) long-term hydrologic monitoring to evaluate the efficacy of LID interventions.
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Cidades , Hidrologia , Chuva , Rios , Filtração/instrumentação , Modelos Teóricos , Água , Movimentos da ÁguaRESUMO
Managers of aquatic resources benefit from indices of habitat quality that are reproducible and easy to measure, demonstrate a link between habitat quality and biota health, and differ between human-impacted (i.e., managed) and reference (i.e., nonimpacted or minimally impacted) conditions. The instability index (ISI) is an easily measured index that describes the instability of a streambed by relating the tractive force of a stream at bankfull discharge to the median substrate size. Previous studies have linked ISI to biological condition but have been limited to comparisons of sites within a single stream or among a small number of streams. We tested ISI as an indicator of human impact to habitat and biota in mountain streams of the northwestern USA. Among 1428 sites in six northwestern states, ISI was correlated with other habitat measures (e.g., residual pool depth, percent fine sediment) and indices of biotic health (e.g., number of intolerant macroinvertebrate taxa, fine sediment biotic index) and differed between managed and reference sites across a range of stream types and ecoregions. While ISI could be useful in mountain streams throughout the world, this index may be of particular interest to aquatic resource managers in the northwestern USA where a large dataset, from which ISI can be calculated, exists.
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Ecologia/métodos , Ecossistema , Rios , Algoritmos , Animais , Monitoramento Ambiental , Sedimentos Geológicos , Invertebrados , Noroeste dos Estados Unidos , SalmonidaeRESUMO
Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3 glomerulopathy (C3G), a rare glomerular disease. The Kidney Health Initiative convened a panel of experts in C3G to ( 1 ) assess the data supporting the use of the prespecified trial end points as measures of clinical benefit and ( 2 ) opine on efficacy findings they would consider compelling as treatment(s) of C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work Group reviewed the available evidence and uncertainties for the association between the three prespecified end points-( 1 ) proteinuria, ( 2 ) eGFR, and ( 3 ) histopathology-and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed end points they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, evidence, and uncertainties, supporting the end points. Given the limitations of the available data, the work group was unable to define a minimum threshold for change in any of the end points that might be considered clinically meaningful. The work group concluded that a favorable treatment effect on all three end points would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three end points if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the end points in the aforementioned trials.
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The aims of this study were to 1) determine whether renal localization of aliskiren and its antihypertensive and renoprotective effects persist after administration of the drug is stopped and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg·kg(-1)·day(-1) sc; osmotic minipumps) or enalapril (18 mg/l in drinking water). After a 2-wk treatment, dTGR were assigned to either continued treatment with aliskiren ("continued"), or to cessation of their respective treatment ("stopped") for a 3-wk washout. One week of treatment with aliskiren and enalapril reduced blood pressure and albuminuria vs. baseline. After cessation of either treatment, blood pressure had returned to pretreatment levels and albuminuria remained relatively low for 1 wk, but rose thereafter similarly in both groups. In contrast, renal mRNA for transforming growth factor-ß and renal collagen IV was reduced by aliskiren (continued and stopped groups), but not after cessation of enalapril. Similar patterns were found for collagen IV protein expression. Even 3 wk after stopping aliskiren treatment, renal levels of the drug exceeded its IC50, whereas enalaprilat was not detected. To localize aliskiren accumulation, Wistar rats were treated with [(3)H]-aliskiren for 7 days. Autoradiography demonstrated specific labeling in glomeruli, arterioles, and afferent arterioles as well as in the distal nephron. Labeling could still be observed even after 7 days' washout. These results suggest that the renophilic properties of aliskiren are different from enalapril and could have contributed to the renoprotective mechanism of this renin inhibitor.
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Amidas/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Fumaratos/farmacologia , Rim/efeitos dos fármacos , Renina/antagonistas & inibidores , Albuminúria/metabolismo , Animais , Rim/metabolismo , Masculino , Ratos , Ratos Transgênicos , Ratos Wistar , Renina/metabolismoRESUMO
Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme inhibitors). In the present study, we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin). Diabetic mice were treated with insulin, aliskiren (a renin inhibitor), benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps. Significant impairment in diastolic and systolic cardiac functions was observed in diabetic mice, which was completely prevented by all three RAS (renin-angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes increased cardiac PRR (prorenin receptor) expression and nuclear translocation of PLZF (promyelocytic zinc finger protein), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by PRR represented a novel mechanism in diabetic cardiomyopathy. Differential effects of the three agents on oxidative stress, cytokines and PRR expression suggested subtle differences in their mechanisms of action.
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Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/enzimologia , Coração/fisiopatologia , Renina/antagonistas & inibidores , Amidas/administração & dosagem , Animais , Benzazepinas/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Fumaratos/administração & dosagem , Coração/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Renina/metabolismo , Tetrazóis/administração & dosagem , Valina/administração & dosagem , Valina/análogos & derivados , Valsartana , Receptor de Pró-ReninaRESUMO
BACKGROUND: Retained surgical items (RSIs) are rare but serious events associated with significant morbidity and costs. We assessed the effectiveness of radiofrequency (RF) detection technology and Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) in reducing the incidence of RSIs. STUDY DESIGN: All RSIs reported to the New York Patient Occurrence Reporting and Tracking System at five large urban teaching hospitals from 2007 to 2017 were analyzed. In 2012, TeamSTEPPS training was provided to all perioperative staff at each site, and use of RF detection became required in all procedures. The incidence of events before and after the interventions were compared using odds ratios. RESULTS: A total of 997,237 operative procedures were analyzed. After the interventions, the incidence of RSIs decreased from 11.66 to 5.80 events per 100,000 operations (odds ratio [OR] [95% CI] = 0.50 [0.32 to 0.78]). The frequency of RSIs involving RF-detectable items decreased from 5.21 to 1.35 events per 100,000 operations (OR [95% CI] = 0.26 [0.11 to 0.60]). The difference in RSIs involving non-RF-detectable surgical items was not statistically significant. CONCLUSIONS: The incidence of RSIs was significantly lower during the time period after implementing RF detection technology and after TeamSTEPPS training, primarily driven by a decrease in retained RF-detectable items. RF detection technology may be worth pursuing for hospitals looking to decrease RSI frequency. The benefit of TeamSTEPPS training alone may not result in a reduction of RSIs.
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Corpos Estranhos , Corpos Estranhos/epidemiologia , Corpos Estranhos/etiologia , Corpos Estranhos/prevenção & controle , Hospitais , Humanos , Incidência , Segurança do Paciente , Comportamento de Redução do RiscoRESUMO
BACKGROUND/AIMS: Altered extracellular matrix (ECM) remodeling and podocyte apoptosis are characteristic features of diabetic nephropathy (DN). Aliskiren (ALI) inhibits the renin-catalyzed conversion of angiotensinogen to angiotensin I. This study tested ALI's effect on podocyte ECM accretion and survival in a high-glucose environment in vitro. METHODS: Conditionally immortalized mouse podocytes were incubated in normal glucose (NG; 5.5 mM) or high glucose (HG; 40 mM) for 24-48 h with and without ALI (20 nM). Real-time RT-PCR was performed for fibronectin (FN), collagen α5(type IV) (Cola5IV), matrix metalloproteinases 2 and 9 (MMP2 and MMP9), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP1 and TIMP2). Western blots were performed for FN, Cola5IV, MMP2, MMP9, TIMP1 and cleaved (activated) caspase-3. RESULTS: ALI significantly reduced the mRNA and protein levels of FN, Cola5IV and TIMP1, and the mRNA of TIMP2 and cleaved caspase-3. ALI had no effect on MMP2 mRNA or protein or MMP9 mRNA tested under HG conditions. Under NG conditions, ALI had no effect on FN, Cola5IV, MMP2, MMP9 and activated caspase-3 proteins. ALI decreased the activated caspase-3 protein and evidence of apoptosis by TUNEL staining observed in podocytes cultured under HG conditions. CONCLUSION: These results show for the first time that renin inhibition with ALI mitigates the profibrotic and apoptotic effects of HG in cultured podocytes. These data strengthen the therapeutic rationale for renin inhibition with ALI beyond its hemodynamic effects.
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Amidas/farmacologia , Apoptose/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fumaratos/farmacologia , Glucose/farmacologia , Podócitos/efeitos dos fármacos , Renina/antagonistas & inibidores , Animais , Células Cultivadas , Colágeno Tipo IV/efeitos dos fármacos , Nefropatias Diabéticas/fisiopatologia , Fibronectinas/efeitos dos fármacos , Metaloproteinases da Matriz/biossíntese , Podócitos/metabolismo , RNA Mensageiro/metabolismoRESUMO
Simulation has become an integral part of physician education, and abundant evidence confirms that simulation-based education improves learners' skills and behaviors and is associated with improved patient outcomes. The resources required to implement simulation-based education, however, have led some stakeholders to question the overall value proposition of simulation-based education. This paper summarizes the information from a special panel on this topic and defines research priorities for the field. Future work should focus on both outcomes and costs, with robust measurement of resource investments, provider performance (in both simulation and real settings), patient outcomes, and impact on the health care organization. Increased attention to training practicing clinicians and health care teams is also essential. Clarifying the value proposition of simulation-based education will require a major national effort with funding from multiple sponsors and active engagement of a variety of stakeholders.
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Educação Médica/métodos , Cirurgia Geral/educação , Treinamento por Simulação , Competência Clínica , Educação Médica/economia , Educação Médica/normas , Cirurgia Geral/economia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Pesquisa , Treinamento por Simulação/economia , Treinamento por Simulação/normas , Estados UnidosRESUMO
BACKGROUND: The surgical management of patients with morbid obesity (body mass index ≥ 40) is notable for a relatively high risk of complications. To address this problem, a perioperative care map was developed using precautions and best practices commonly employed in bariatric surgery. It requires additional medical assessments, sleep apnea surveillance, more stringent guidelines for anesthetic management, and readily available bariatric operating room equipment, among other items. This care map was implemented in 2013 at 4 major urban teaching hospitals for use in patients undergoing all types of nonambulatory surgery with a body mass index greater than 40 kg/m2. The impact on patient outcomes was evaluated. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to compare 30-day outcomes of morbidly obese patients before the year 2013 and after the years 2015 care-map implementation. In addition, trends in 30-day outcomes for morbidly obese patients were compared with those for non-obese patients. RESULTS: Morbidly obese patients, between 2013 and 2015, saw an adjusted decrease in the rate of unplanned return to the operating room (OR = 0.49; P = .039), unplanned readmission (OR = 0.57; P = .006), total duration of stay (-0.87 days; P = .009), and postoperative duration of stay (-0.69 days; P = .007). Of these, total duration of stay (-0.86 days; P = .015), and postoperative duration of stay (-0.69 days; P = .012) improved significantly more for morbidly obese patients than for nonmorbidly obese patients. CONCLUSION: Outcomes in morbidly obese patients improved from 2013 to 2015. Implementation of a perioperative care map may have contributed to these improvements. The care map should be further investigated and considered for more widespread use.
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Obesidade Mórbida , Assistência Perioperatória , Adulto , Procedimentos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Few guidelines exist on safe prescription of postoperative analgesia to obese patients undergoing ambulatory surgery. This study examines the preferences of providers in the standard treatment of postoperative pain in the ambulatory setting. METHODS: Providers from five academic medical centers within a single US city were surveyed from May-September 2015. They were asked to provide their preferred postoperative analgesic routine based upon the predicted severity of pain for obese and non-obese patients. McNemar's tests for paired observations were performed to compare prescribing preferences for obese vs. non-obese patients. Fisher's exact tests were performed to compare preferences based on experience: > 15 years vs. ≤15 years in practice, and attending vs. resident physicians. RESULTS: A total of 452 providers responded out of a possible 695. For mild pain, 119 (26.4%) respondents prefer an opioid for obese patients vs. 140 (31.1%) for non-obese (p = 0.002); for moderate pain, 329 (72.7%) for obese patients vs. 348 (77.0%) for non-obese (p = 0.011); for severe pain, 398 (88.1%) for obese patients vs. 423 (93.6%) for non-obese (p < 0.001). Less experienced physicians are more likely to prefer an opioid for obese patients with moderate pain: 70 (62.0%) attending physicians with > 15 years in practice vs. 86 (74.5%) with ≤15 years (p = 0.047), and 177 (68.0%) attending physicians vs. 129 (83.0%) residents (p = 0.002). CONCLUSIONS: While there is a trend to prescribe less opioid analgesics to obese patients undergoing ambulatory surgery, these medications may still be over-prescribed. Less experienced physicians reported prescribing opioids to obese patients more frequently than more experienced physicians.
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BACKGROUND: Teamwork in the operating room decreases the risk of preventable patient harm. Observation in the operating room allows for evaluation of compliance with best-practice surgical guidelines. This study examines the relative ability of video and live observation to promote operating room teamwork. METHODS: Video and audio cameras were installed in 2014 into all operating rooms at an 875-bed, urban teaching hospital. Recordings were chosen at random for review by an internal quality improvement team. Concurrently, live observers were deployed into a random selection of operations. A customized tool was used to evaluate compliance to TeamSTEPPS skills during surgical briefs and debriefs. RESULTS: A total of 1,410 briefs were evaluated: 325 (23%) through live observation and 1,085 (77%) through video; 1,398 debriefs were evaluated: 166 (12%) live and 1,232 (88%) video. For briefs, greater compliance was observed under live observation compared to video for recognition of team membership (87% vs 44%, P<.001), anticipation of complex procedural events (61% vs 45%, P<.001), and monitoring of resources (58% vs 42%, P<.001). For debriefs, greater compliance was observed under live observation for determination of team structure (90% vs 60%, P<.001), establishment of a leader (70% vs 51%, P<.001), postoperative planning (77% vs 48%, P<.001), case review and feedback (49% vs 33%, P<.001), team engagement (64% vs 41%, P<.001), and check back (61% vs 46%, P<.001) compared to video. CONCLUSION: Video observations may not be as effective as evaluating live performance in promoting teamwork in the OR. Live observation enables immediate feedback, which may improve behavior and decrease barriers to compliance with surgical safety practices.
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Observação , Equipe de Assistência ao Paciente , Procedimentos Cirúrgicos Operatórios , Gravação em Vídeo , Protocolos Clínicos , Fidelidade a Diretrizes , Humanos , Segurança do PacienteRESUMO
We studied the effects of extremely low-dose human renin inhibition (aliskiren) with low angiotensin II receptor blockade (losartan) in a novel double-transgenic rat model harbouring both human renin and angiotensinogen genes. We found that low-dose aliskiren and low-dose losartan effectively reduced mortality and target-organ damage with minimal, non-significant, effects on blood pressure (BP). Our data suggest that renin-angiotensin system (RAS) inhibition ameliorates target-organ damage in an Ang II-driven model of hypertension. Direct renin inhibition is equally efficacious in this regard. Our study does not fully answer the question of BP-lowering versus RAS inhibition. This question is important and was at least partially addressed with our low-dose model.