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On February 28, 2020, public health officials in the Seattle area were informed of a Covid-19 infection at a long-term care facility. An investigation identified 167 infected persons associated with the facility, including residents, health care personnel, and visitors; more than a third of the 101 residents identified died.

In this trial, over 23,000 patients with out-of-hospital cardiac arrest were assigned to standard CPR with a chest compression-to-ventilation ratio of 30:2 or to continuous chest compressions. There was no significant between-group difference in survival to hospital discharge. Standard cardiopulmonary resuscitation (CPR) consists of manual chest compressions to maintain blood flow and positive-pressure ventilation to maintain oxygenation until spontaneous circulation is restored. 1 Chest compressions are interrupted frequently by ventilations given as rescue breathing during the treatment of out-of-hospital cardiac arrest. 2 – 4 These interruptions reduce blood flow and potentially reduce the effectiveness of CPR. 5 One strategy to reduce the interruption of compressions is to provide asynchronous positive-pressure ventilation while not pausing for ventilations. The interruption of chest compressions has been associated with decreased survival in animals with cardiac arrest. 6 In nonasphyxial arrest, continuous compressions were as effective as compressions . . .

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.

Several tyrosine kinase inhibitors have activity in Ph-positive chronic and acute leukemia, but resistant disease and unacceptable side effects may limit efficacy. Ponatinib showed a high level of activity in a phase 2 study of tyrosine kinase inhibitor–resistant disease but was associated with arterial thrombosis. Patients with newly diagnosed chronic myeloid leukemia (CML) frequently receive imatinib. Although initial response rates are high, imatinib fails in up to 40% of patients because of disease resistance, frequently because of BCR-ABL kinase domain mutations or unacceptable side effects. 1 , 2 Patients who discontinue imatinib may have a response to second-generation tyrosine kinase inhibitors. However, 37 to 52% of patients do not have a response, 3 – 8 and 23 to 26% of patients have an initial major cytogenetic response that is lost by 2 years. 3 , 9 The prognosis for these patients is very poor. With the exception of the small number . . .

Abstract Rationale Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system—pre-hospital emergency care—is unknown. Objectives We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. Methods Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. Measurements and Main Results Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). Conclusions EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.

Objective To investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation outside hospital increases the proportion of subjects who achieved prehospital return of spontaneous circulation.Design A cluster-randomised trial.Subjects 1586 people having cardiac arrest outside hospital in whom resuscitation was attempted by emergency medical services (771 procedures without feedback, 815 with feedback).Setting Emergency medical services from three sites within the Resuscitation Outcomes Consortium in the United States and Canada.Intervention Real-time audio and visual feedback on cardiopulmonary resuscitation (CPR) provided by the monitor-defibrillator.Main outcome measure Prehospital return of spontaneous circulation after CPR.Results Baseline patient and emergency medical service characteristics did not differ between groups. Emergency medical services muted the audible feedback in 14% of cases during the period with feedback. Compared with CPR clusters lacking feedback, clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided (64% v 66%, cluster-adjusted difference 1.9 (95% CI 0.4 to 3.4)), increased compression depth (38 v 40 mm, adjusted difference 1.6 (0.5 to 2.7)), and decreased proportion of compressions with incomplete release (15% v 10%, adjusted difference −3.4 (−5.2 to −1.5)). However, frequency of prehospital return of spontaneous circulation did not differ according to feedback status (45% v 44%, adjusted difference 0.1% (−4.4% to 4.6%)), nor did the presence of a pulse at hospital arrival (32% v 32%, adjusted difference −0.8 (−4.9 to 3.4)), survival to discharge (12% v 11%, adjusted difference −1.5 (−3.9 to 0.9)), or awake at hospital discharge (10% v 10%, adjusted difference −0.2 (−2.5 to 2.1)).Conclusions Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines. However, these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes.Trial Registration Clinical Trials NCT00539539

Background The Cerebral Performance Category (CPC) score is widely used in research and quality assurance to assess neurologic outcome following cardiac arrest. However, little is known about the inter- and intra-reviewer reliability of the CPC. Methods We undertook an investigation to assess the inter-reviewer and source document reliability of the CPC among a cohort of survivors from out-of-hospital ventricular fibrillation cardiac arrest (n = 131) in a large metropolitan area between November 1, 2003 and December 31, 2005. Subjects with a CPC of 1 or 2 were classified as favorable outcome and those with CPC 3 or greater were classified as unfavorable outcome. One abstractor first used the discharge summary alone to determine the CPC. All 3 abstractors independently reviewed the entire hospital record. Reliability was assessed by determining the proportion of determinations that agreed between abstractors and the respective kappa statistics. We also evaluated the implications for determining survival with favorable neurological outcome when survival to hospital discharge was 20% and 30%. Results When the entire hospital record was used to determine CPC, favorable neurologic outcome (CPC 1 or 2) was recorded in 92% by abstractor 1, 89% by abstractor 2, and 74% by abstractor 3. Agreement was 96% (kappa = 0.78) between abstractors 1 and 2, 84% (kappa = 0.49) between abstractors 2 and 3, 82% (kappa = 0.38) between abstractors 1 and 3. The 3-way kappa was 0.50. Agreement was 90% (kappa = 0.71) between the discharge summary alone and the entire hospital record. If the results from review of the entire record are applied to a circumstance where survival to discharge is 20%, favorable neurologic status would occur in 18.4% for abstractor 1, 17.8% for abstractor 2, and 14.8% for abstractor 3. For survival to hospital discharge of 30%, favorable neurologic status would occur in 27.6% for abstractor 1, 26.7% for abstractor 2, and 22.2% for abstractor 3. Conclusions In this cohort study of survivors of out-of-hospital ventricular fibrillation cardiac arrest, the use of the CPC to classify favorable versus unfavorable neurological status at hospital discharge produced variable inter- and intra-reviewer agreement. The findings provide useful context to interpret outcome evaluations that report CPC.

Several retrospective studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. We thus prospectively screened for PAOD in patients with chronic phase chronic myeloid leukemia (CP CML) being treated with tyrosine kinase inhibitors (TKI), including imatinib and nilotinib. One hundred and fifty-nine consecutive patients were evaluated for clinical and biochemical risk factors for cardiovascular disease. Non-invasive assessment for PAOD included determination of the ankle-brachial index (ABI) and duplex ultrasonography. A second cohort consisted of patients with clinically manifest PAOD recruited from additional collaborating centers. Pathological ABI were significantly more frequent in patients on first-line nilotinib (7 of 27; 26%) and in patients on second-line nilotinib (10 of 28; 35.7%) as compared with patients on first-line imatinib (3 of 48; 6.3%). Clinically manifest PAOD was identified in five patients, all with current or previous nilotinib exposure only. Relative risk for PAOD determined by a pathological ABI in first-line nilotinib-treated patients as compared with first-line imatinib-treated patients was 10.3. PAOD is more frequently observed in patients receiving nilotinib as compared with imatinib. Owing to the severe nature of clinically manifest PAOD, longitudinal non-invasive monitoring and careful assessment of risk factors is warranted.