Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 126
Filtrar
1.
Braz J Anesthesiol ; 71(1): 50-57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33712254

RESUMO

BACKGROUND: Laparoscopic surgical approaches enhance recovery, reduce postoperative pain, and shorten hospital length-of-stay. Nevertheless, increased intra-abdominal pressure is associated with decreased renal blood flow, renal hypoxia and acute kidney injury. When combined with Trendelenburg positioning, renal function may further deteriorate. We tested the primary hypothesis that the combination of laparoscopic surgical approach and Trendelenburg position is associated with larger reductions in estimated Glomerular Filtration Rate (eGFR) within the initial 48 postoperative hours compared to open surgery without Trendelenburg positioning. Secondarily, we tested, if laparoscopic procedures are associated with greater incidence of postoperative acute kidney injury. METHODS: Adults who had laparoscopic colorectal surgery in Trendelenburg position at the Cleveland Clinic Main Campus from 2009 to 2016 were propensity-matched to patients who had comparable open procedures. Patients with pre-existing renal impairment were excluded. RESULTS: Among 7,357 eligible patients, 1,846 laparoscopic cases with Trendelenburg were matched to 1,846 open cases. No association was found between laparoscopic approach and postoperative eGFR. A significant protective effect of the laparoscopic procedure on the odds of having AKI was found. Patients who had laparoscopic surgeries were an estimated 0.70 (95% CI 0.55, 0.90, pHolm-adj = 0.006) times as likely to have AKI as open surgical patients. CONCLUSION: Despite compelling potential mechanisms, laparoscopic approach with Trendelenburg position in adult colorectal surgeries did not worsen postoperative eGFR, and actually reduced postoperative acute kidney injury. Given the other advantages of laparoscopic surgery, the approach should not be avoided for concerns about renal injury.

2.
J Cutan Med Surg ; : 1203475421999331, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33715454

RESUMO

BACKGROUND: Knowledge about the clinical features of Darier disease, an orphan autosomal-dominant genetic disorder, is sparse and has been evaluated only in few studies. OBJECTIVES: To investigate the clinical features of a large group of patients with Darier disease, and to explore for associations between disease characteristics and severity of the disease. METHODS: Seventy-six individuals with Darier disease were evaluated utilizing a structured questionnaire-based interview, a physical examination, and a retrospective assessment of their medical records. RESULTS: The most frequent locations of lesions were hands (99%) and fingernails (93%). Wart-like lesions on the hands were more visible after soaking them in water for 5 minutes, we therefore named this phenomenon the "wet hand sign". Oral involvement was found in 43% of patients, while 48% of women and 16% of men showed genital lesions. Patients with severe Darier disease had a tenfold greater risk of developing genital lesions than those with mild disease (P = .01). Most patients (88%) in our study exhibited a combination of the four types of the disease patterns of distribution (flexural, seborrheic, nevoid, and acral). CONCLUSIONS: Documentation of disease on the hands and fingernails provides a highly sensitive means to aid in the diagnosis of Darier disease. It is important to evaluate mucosal lesions including genital and oral mucosa.

3.
Exp Dermatol ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33786896

RESUMO

Autosomal recessive congenital ichthyosis (ARCI) is a rare and heterogeneous skin cornification disorder presenting with generalized scaling and varying degrees of erythema. Clinical manifestations range from lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) through the most severe form of ARCI, Harlequin ichthyosis (HI). We used homozygosity mapping, whole exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotype-phenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI-associated genes including TGM1 (21%), CYP4F22 (18%), ALOX12B (14%), ABCA12 (10%), ALOXE3 (6%), NIPAL4 (5%), PNPLA1 (3%), LIPN (2%) and SDR9C7 (2%). In 19% of cases, no mutation was identified. Our cohort revealed a higher prevalence of CYP4F22 and ABCA12 pathogenic variants and a lower prevalence of TGM1 and NIPAL4 variants, as compared to data obtained in other regions of the world. Most variants (89%) in ALOX12B were associated with CIE and were the most common cause of ARCI among patients of Muslim origin (26%). Palmoplantar keratoderma associated with fissures was exclusively a result of pathogenic variants in TGM1. To our knowledge, this is the largest cohort study of ARCI in the Middle Eastern population reported to date. Our data demonstrate the importance of population-tailored mutation screening strategies and shed light upon specific genotype-phenotype correlations.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33411992

RESUMO

Fremanezumab (AJOVY; Teva Pharmaceutical Industries Ltd, Netanya, Israel), approved for the preventive treatment of migraine, is available as a subcutaneous injection either once a month or once every 3 months using an autoinjector or a prefilled syringe. The present study evaluated the pharmacokinetic (PK) bioequivalence of a single subcutaneous injection of fremanezumab 225 mg administered using an autoinjector compared to a prefilled syringe in healthy volunteers. Blood samples for PK and antidrug antibodies were collected before and after dosing. Safety and tolerability assessments included physical examinations, adverse event reporting, laboratory evaluations, and immunogenicity. Following single-dose administration, the mean concentration-time profiles for the 2 treatment groups (autoinjector, n = 106; and prefilled syringe, n = 110) were similar. The point estimates for the back-transformed ratio (autoinjector/prefilled syringe) of geometric least squares means of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the time of the last measurable drug concentration, and area under the plasma concentration-time curve from time 0 extrapolated to infinity were 1.03, 1.04, and 1.05, respectively, with the 90% confidence intervals entirely contained within bioequivalence margins of 0.8 to 1.25. For both groups, median time to maximum observed concentration was 5 days and mean terminal elimination half-life was approximately 29 days. Treatment-related adverse events were reported by 39 (36%) subjects in the autoinjector group and 26 (24%) in the prefilled syringe group, and the majority were nonserious injection site reactions. The incidence of treatment-emergent antidrug antibody response was low and evenly distributed between the autoinjector (n = 3; 3%) and prefilled syringe (n = 4; 4%) groups. These results indicate that the fremanezumab autoinjector presentation provides an easy-to-use bioequivalent PK profile with a similar safety and tolerability profile to that of the prefilled syringe.

5.
Anesth Analg ; 132(3): 866-877, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433116

RESUMO

BACKGROUND: Anesthesiologists typically care for patients having a broad range of procedures. Outcomes might be improved when care is provided by caregivers experienced in particular types of surgery. We tested the hypothesis that intraoperative care provided by pairs of anesthesia caregivers having significant experience with a particular type of surgery reduces a composite of in-hospital death and 6 serious complications, including bleeding, cardiac, gastrointestinal, infectious, respiratory, and urinary complications, compared to care provided by pairs of anesthesia caregivers with less experience. METHODS: We included patients having surgery lasting at least 30 minutes. Using cluster analysis, attending anesthesiologists, and Certified Registered Nurse Anesthetists (CRNAs) were identified as experienced or inexperienced caregivers for each type of surgery at the case level. We then compared surgeries for which anesthesia was provided by a pair of experienced caregivers versus a pair of inexperienced caregivers on our composite outcome. We estimated the average relative effect (ie, the exponentiated average log odds ratio) of receiving anesthesia from an experienced versus inexperienced caregiver pair across the 7 components of the composite outcome using a generalized estimating equation (GEE) model to adjust for between-component correlation and with inverse propensity score weighing to adjust for potential confounding from a host of variables. RESULTS: A total of 8968 patients who received anesthesia care by an experienced pair were compared with 25,361 patients who received care from an inexperienced pair, adjusting for potential confounding. The incidence of composite complications (ie, any component event) was 7.6% (677/8968) for experienced pairs and 12% (2976/25,361) for inexperienced pairs (P < .001). Care by experienced pairs of caregivers was associated with lower odds of the composite outcome with an estimated average relative effect odds ratio across the individual components of 0.61 (95% confidence interval [CI], 0.54-0.71), P < .001. Among the 7 components of the primary outcome, experienced pairs of providers had significantly lower estimated odds of bleeding, infection, and mortality. CONCLUSIONS: Anesthesia care by experienced pairs was associated with fewer bleeding complications, fewer infections, shorter hospitalization, and reduced in-hospital mortality.


Assuntos
Anestesiologistas , Competência Clínica , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias/prevenção & controle , Especialização , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Mortalidade Hospitalar , Humanos , Cuidados Intraoperatórios , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/mortalidade , Fatores de Tempo , Resultado do Tratamento
6.
Cell Rep ; 33(12): 108531, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33357440

RESUMO

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, with a protein-dependent effect on magnitude. Finally, we demonstrate that targets are derepressed in CELF6-mutant mice, and at least two key CNS proteins, FOS and FGF13, show altered protein expression levels and localization. Our works find, in addition to previously identified roles in splicing, that CELF6 is associated with repression of its CNS targets via the 3' UTR in vivo.

7.
Asian J Anesthesiol ; 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-33176407

RESUMO

BACKGROUND: Extended-release local anesthetics allow for prolonged analgesia after a single administration. Although Asians demonstrate different pain thresholds than Caucasians, whether they have different postoperative local anesthetic analgesic effects has not been elucidated. OBJECTIVE: We aimed to compare the postoperative analgesic efficacy of liposomal bupivacaine on Asian and Caucasian adults, and the incidence of local anesthetic systemic toxicity (LAST) syndrome. METHODS: We conducted a retrospective, assessor-blinded cohort study of adult patients who received liposomal bupivacaine for surgery between 2012 and 2018. Asians and Caucasians were matched in a 1:1 ratio by clinical characteristics and surgery type. The primary outcome was pain management, defined as average pain score and opioid consumption during the initial 72 postoperative hours. The secondary outcome was the incidence of LAST syndrome. Reviewers were blinded to the ethnicity of the patient. RESULTS: After 1:1 propensity score matching, 130 Asians and 129 Caucasians were analyzed. All confounding variables were balanced, except for higher body mass index in the Asian group. Pain scores were lower (adjusted mean difference of -0.50 [97.5% CI, -0.98, -0.01]; superiority p = 0.011) and opioid consumption was not greater (geometric means ratio, 0.61 [97.5% CI, 0.36, 1.04]; non-inferiority p < 0.001) in Asian patients compared to Caucasian patients. Only one Caucasian patient was judged as having a potential case of LAST syndrome. The length of hospital stay and the incidence of additional complications were not different between the groups. CONCLUSION: Asian adults receiving liposomal bupivacaine as part of multimodal perioperative analgesia demonstrated lower pain scores compared to matching Caucasians, despite not having greater opioid consumption.

8.
Curr Protoc Cell Biol ; 89(1): e115, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33044803

RESUMO

Biochemical methods can reveal stable protein-protein interactions occurring within cells, but the ability to observe transient events and to visualize the subcellular localization of protein-protein interactions in cells and tissues in situ provides important additional information. The Proximity Ligation Assay® (PLA) offers the opportunity to visualize the subcellular location of such interactions at endogenous protein levels, provided that the probes that recognize the target proteins are within 40 nm. This sensitive technique not only elucidates protein-protein interactions, but also can reveal post-translational protein modifications. The technique is useful even in cases where material is limited, such as when paraffin-embedded clinical specimens are the only available material, as well as after experimental intervention in 2D and 3D model systems. Here we describe the basic protocol for using the commercially available Proximity Ligation Assay™ materials (Sigma-Aldrich, St. Louis, MO), and incorporate details to aid the researcher in successfully performing the experiments. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Proximity ligation assay Support Protocol 1: Antigen retrieval method for formalin-fixed, paraffin-embedded tissues Support Protocol 2: Creation of custom PLA probes using the Duolink™ In Situ Probemaker Kit when commercially available probes are not suitable Basic Protocol 2: Imaging, quantification, and analysis of PLA signals.

9.
BMC Anesthesiol ; 20(1): 262, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050885

RESUMO

BACKGROUND: The Coronavirus infectious disease 2019 (COVID-19) brings anesthesiologists and intensive care physicians to the mainstay of clinical workload and healthcare managements' focus. There are approximately 900 anesthesiologists in Israel, working in non-private hospitals. This nationwide cross-sectional study evaluated the readiness and involvement of anesthesia departments in Israel in management of the COVID-19 pandemic. The impact on anesthesiologists' health, workload, and clinical practices were also evaluated. METHODS: An online questionnaire was distributed to all of anesthesia department chairs in Israel on April 14th. Each response was identifiable on the hospital level only. Informed consent was waived since no patient data were collected. RESULTS: Response rate was 100%. A decrease of at least 40% in operating-room activity was reported by two-thirds of the departments. Anesthesiologists are leading the treatment of COVID-19 patients in 19/28 (68%) Israeli hospitals. Israel Society of Anesthesiologists' recommendations regarding intubation of COVID-19 patients were strictly followed (intubations performed by the most experienced available physician, by rapid-sequence induction utilizing video-laryngoscopy, while minimizing the number of people in the room - about 90% compliance for each). Anesthesiologists in most departments use standard personal protective equipment when caring for COVID-19 patients, including N95 masks, face shields, and water-proof gowns. Only one anesthesiologist across Israel was diagnosed with COVID-19 (unknown source of transmission). All department chairs reported emerging opportunities that advance the anesthesia profession: implementation of new technologies and improvement in caregivers' clinical capabilities (68% each), purchase of new equipment (96%), and increase in research activity (36%). CONCLUSIONS: This nationwide cross-sectional study had a complete response rate and therefore well-represents the anesthesia practice in Israel. We found that Israeli anesthesia departments are generally highly involved in the health system efforts to cope with the COVID-19 pandemic. Anesthesia and airway management are performed in a remarkably comparable manner and with proper protection of caregivers. Ambulatory anesthesia activity has dramatically decreased, but many departments find opportunities for improvement even in these challenging times.


Assuntos
Serviço Hospitalar de Anestesia/organização & administração , Anestesiologistas/organização & administração , Anestesiologia/organização & administração , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Manuseio das Vias Aéreas/métodos , Anestesia/métodos , Estudos Transversais , Humanos , Intubação Intratraqueal/métodos , Israel/epidemiologia , Salas Cirúrgicas/organização & administração , Pandemias , Inquéritos e Questionários
10.
Br J Anaesth ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33051083

RESUMO

BACKGROUND: Myocardial infarction is the most common postoperative major vascular complication. Perioperative anaemia may contribute to cardiac supply-demand mismatch, and therefore myocardial injury. We therefore tested the hypothesis that the lowest in-hospital postoperative haemoglobin concentration is associated with a composite of non-fatal myocardial infarction and all-cause mortality within the first 30 days after noncardiac surgery. METHODS: We conducted a retrospective analysis of patients enrolled in the PeriOperative Ischemic Evaluation-2 (POISE-2) trial. We assessed the association between the lowest postoperative haemoglobin concentration during the initial hospitalisation and a composite of non-fatal myocardial infarction (Third Universal Definition) and all-cause mortality within 30 postoperative days, using a multivariable logistic regression model. RESULTS: We analysed 7227 patients from POISE-2, of whom 7.8% developed myocardial infarction; 1.5% died within 30 days. The composite primary outcome of non-fatal myocardial infarction and all-cause mortality occurred in 8.9% patients overall, ranging from 16% in patients with postoperative haemoglobin concentrations <88 g L-1 to 4.1% in patients with postoperative haemoglobin >113 g L-1. After adjusting for baseline factors, in patients with a lowest postoperative haemoglobin concentration <110 g L-1, each 10 g L-1 reduction in the lowest postoperative haemoglobin concentration was associated with a 1.46 (95% confidence interval: 1.37-1.56; P<0.001) fold increase in the odds of the composite outcome. In contrast, there was no significant relationship amongst patients with lowest postoperative haemoglobin concentration >110 g L-1. CONCLUSIONS: Postoperative anaemia may be a modifiable risk factor for non-fatal myocardial infarction and all-cause mortality.

11.
Br J Anaesth ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33039122

RESUMO

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply-demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. METHODS: We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml-1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. RESULTS: Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl-1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was <8 g dl-1. The confounder-adjusted hazard ratio [95% confidence interval] for having MINS was 1.29 [1.16-1.42] for every 1 g dl-1 decrease in postoperative haemoglobin in a time-varying covariate analysis. Similar associations were identified in sensitivity analyses. CONCLUSION: Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of, anaemia remains to be determined.

12.
Eur J Hum Genet ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939038

RESUMO

Since 1999, the COCH gene encoding cochlin, has been linked to the autosomal dominant non-syndromic hearing loss, DFNA9, with or without vestibular abnormalities. The hearing impairment associated with the variants affecting gene function has been attributed to a dominant-negative effect. Mutant cochlin was seen to accumulate intracellularly, with the formation of aggregates both inside and outside the cells, in contrast to the wild-type cochlin that is normally secreted. While additional recessive variants in the COCH gene (DFNB110) have recently been reported, the mechanism of the loss-of-function (LOF) effect of the COCH gene product remains unknown. In this study, we used COS7 cell lines to investigate the consequences of a novel homozygous frameshift variant on RNA transcription, and on cochlin translation. Our results indicate a LOF effect of the variant and a major decrease in cochlin translation. This data have a dramatic impact on the accuracy of genetic counseling for both heterozygote and homozygote carriers of LOF variants in COCH.

14.
Saudi J Anaesth ; 14(3): 406-408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32934641

RESUMO

The quadratus lumborum (QL) block provides analgesia to the abdominal wall while sparing the side effects of neuraxial blocks. We describe a case series of eight patients treated with a continuous infusion of local anesthetic via bilateral posterior QL catheters infusion block for analgesia after abdominal surgeries. We found that the median duration of the procedure was 26 min and the median opioid consumption over the first postoperative 72 h was 110 mg of morphine equivalents. The bilateral continuous posterior QL block is a feasible analgesic intervention and can be considered as a component of multimodal analgesic pathways.

15.
Am J Disaster Med ; 15(2): 85-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804388

RESUMO

OBJECTIVE: To determine whether application of a gum-elastic bougie (GEB), a visual stylet used to improve success rates of difficult intubations, reduces the time, and number of attempts to achieve successful intubation while wearing personal protective equipment (PPE). DESIGN: A randomized cross-over study comparing orotracheal intubations performed on an AirMan® Mannequin, using either a semirigid stylet or a GEB, while wearing an active hood with a charcoal impregnated suit and butyl rubber gloves. SETTING: Simulation training field of the Israel Defense Force Medical Corps. PARTICIPANTS: 27 military physicians and 23 paramedics (PMs). INTERVENTIONS: Comparing intubation with and without using the GEB while wearing PPE. MAIN OUTCOME MEASURE(S): Airway (AW) control was considered successful if the "lungs" of the mannequin ex-panded during bag ventilation. Three unsuccessful attempts or a procedure exceeding 60 seconds were regarded as a failure. Correlations between parameters of self-assessment of skills and successful intubation were also determined. RESULTS: With the GEB, success rate was lower (82 percent versus 100 percent, p = 0.002), more attempts were needed (1.4 ± 0.7 versus 1.0 ± 0.2, p = 0.005) and time-to-achieve AW control was longer (43.6 ± 14.6 sec-onds versus 23.1 ± 10.5 seconds, P < 0.001) than without it. Participants with high self-assessment of GEB-assisted AW management skills needed less attempts to perform successful intubation with GEB than participants with low self-assessment (1.0 ± 0.0 versus 1.4 ± 0.8, p = 0.001), but not less time to achieve it. CONCLUSIONS: While donning PPE, the use of GEB (versus semirigid stylets) did not reduce the time or the number of attempts necessary to achieve successful intubation.


Assuntos
Obstrução das Vias Respiratórias/terapia , Intubação Intratraqueal/instrumentação , Equipamento de Proteção Individual , Treinamento por Simulação , Estudos Cross-Over , Desenho de Equipamento , Humanos , Intubação Intratraqueal/métodos , Israel , Manequins , Simulação de Paciente
16.
Intensive Care Med ; 46(10): 1873-1883, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32860069

RESUMO

PURPOSE: Information regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome. METHODS: Between 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)-36 (worst) was assigned to each patient. LUS findings were compared with clinical data. RESULTS: The median baseline total LUS score was 15, IQR [7-20]. Baseline LUS score was 0-18 in 80 (67%) patients, and 19-36 in 40 (33%) patients. The majority had patchy pleural thickening (n = 100; 83%), or patchy subpleural consolidations (n = 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (p = 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0-18. Unadjusted hazard ratio of death for LUS score was 1.08 per point [1.02-1.16], p = 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point [1.05-1.2], p = 0.0008. CONCLUSION: Hospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients' management strategies, as well as resource allocation in case of surge capacity.


Assuntos
Infecções por Coronavirus/patologia , Hospitalização , Pulmão/patologia , Pleura/patologia , Pneumonia Viral/patologia , Respiração Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Coronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Hospitais , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Valores de Referência , /patologia , Medição de Risco , Índice de Gravidade de Doença , Ultrassonografia
17.
JAMA ; 324(4): 350-358, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32721009

RESUMO

Importance: Opioid-induced ventilatory depression and hypoxemia is common, severe, and often unrecognized in postoperative patients. To the extent that nonopioid analgesics reduce opioid consumption, they may decrease postoperative hypoxemia. Objective: To test the hypothesis that duration of hypoxemia is less in patients given intravenous acetaminophen than those given placebo. Design, Setting, and Participants: Randomized, placebo-controlled, double-blind trial conducted at 2 US academic hospitals among 570 patients who were undergoing abdominal surgery, enrolled from February 2015 through October 2018 and followed up until February 2019. Interventions: Participants were randomized to receive either intravenous acetaminophen, 1 g (n = 289), or normal saline placebo (n = 291) starting at the beginning of surgery and repeated every 6 hours until 48 postoperative hours or hospital discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was the total duration of hypoxemia (hemoglobin oxygen saturation [Spo2] <90%) per hour, with oxygen saturation measured continuously for 48 postoperative hours. Secondary outcomes were postoperative opioid consumption, pain (0- 10-point scale; 0: no pain; 10: the most pain imaginable), nausea and vomiting, sedation, minimal alveolar concentration of volatile anesthetic, fatigue, active time, and respiratory function. Results: Among 580 patients randomized (mean age, 49 years; 48% women), 570 (98%) completed the trial. The primary outcome, median duration with Spo2 of less than 90%, was 0.7 (interquartile range [IQR], 0.1-5.1) minutes per hour among patients in the acetaminophen group and 1.1 (IQR, 0.1-6.6) minutes per hour among patients in the placebo group (P = .29), with an estimated median difference of -0.04 (95% CI,-0.18 to 0.11) minutes per hour. None of the 8 secondary end points differed significantly between the acetaminophen and placebo groups. Mean pain scores within initial 48 postoperative hours were 4.2 (SD, 1.8) in the acetaminophen group and 4.4 (SD, 1.8) in the placebo group (difference, -0.28; 95% CI, -0.71 to 0.15); median opioid use in morphine equivalents was 50 mg (IQR, 18-122 mg) and 58 mg (IQR, 24-151 mg) , respectively, with a ratio of geometric means of 0.86 (95% CI, 0.61-1.21). Conclusions and Relevance: Among patients who underwent abdominal surgery, use of postoperative intravenous acetaminophen, compared with placebo, did not significantly reduce the duration of postoperative hypoxemia over 48 hours. The study findings do not support the use of intravenous acetaminophen for this purpose. Trial Registration: ClinicalTrials.gov Identifier: NCT02156154.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Hipóxia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Falha de Tratamento
19.
J Clin Med ; 9(7)2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32708357

RESUMO

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. METHODS: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. RESULTS: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors. CONCLUSIONS: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

20.
Headache ; 60(7): 1376-1391, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445498

RESUMO

OBJECTIVE: Exposure-response (E-R) models were developed to provide a description of the time-course of treatment effect for monthly and quarterly dosing regimens of fremanezumab. BACKGROUND: Fremanezumab is a monoclonal antibody for preventive treatment of episodic migraine (EM) and chronic migraine (CM). In phase 2b and 3 clinical studies of fremanezumab, significant reductions in migraine and headache days and other clinical endpoints were observed for patients with EM and patients with CM. Development of E-R models relating individual-specific measures of drug exposure to clinical endpoints provides a more granular understanding of the expected effects of different doses on therapeutic outcomes by accounting for variability in pharmacokinetic (PK) properties. METHODS: Data from 2 phase 2b and 2 phase 3 studies of adults with EM or CM were used. Individual exposures were calculated from a population PK model and related to monthly migraine days in EM and moderate-severe (M/S) headache days in CM. Model-based stochastic simulations were performed to compare predicted responses for the various treatment regimens. RESULTS: The effect of average fremanezumab concentration compared to placebo on the reduction in migraine days and M/S headache days was predicted by the models to be similar for 225 mg monthly and 675 mg once quarterly over time for both EM and CM patients. Both regimens were associated with better response than placebo. A similar percent of EM and CM responders was predicted across the range of observed body weights. CONCLUSIONS: Exposure-response evaluations showed that both monthly (225 mg) and quarterly (675 mg) fremanezumab dosing regimens were appropriate in achieving clinical benefit in adult patients with EM or CM.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...