A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants.

Anticoagulation carries a tremendous therapeutic advantage in reducing morbidity and mortality with venous thromboembolism and atrial fibrillation. For over six decades, traditional anticoagulants like low molecular weight heparin and vitamin K antagonists like warfarin have been used to achieve therapeutic anticoagulation. In the past decade, multiple new direct oral anticoagulants have emerged and been approved for clinical use. Since their introduction, direct oral anticoagulants have changed the landscape of anticoagulants. With increasing indications and use in various patients, they have become the mainstay of treatment in venous thromboembolic diseases. The safety profile of direct oral anticoagulants is better or at least similar to warfarin, but several recent reports are focusing on spontaneous hemorrhages with direct oral anticoagulants. This narrative review aims to summarize the incidence of spontaneous hemorrhage in patients treated with direct oral anticoagulants and also offers practical management strategies for clinicians when patients receiving direct oral anticoagulants present with bleeding complications.

Perioperative management of anticoagulation.

Periprocedural management of the anticoagulated patient can be as easy as continuing warfarin for a low bleeding risk procedure, holding a direct oral anticoagulant for 1 day prior and resuming 1 day later or as complex as emergent reversal with prothrombin complex concentrate, idarucizumab, or andexanet alfa. Patient-specific factors for thromboembolic risk and procedural bleeding risk determine timing of anticoagulation hold prior to and resumption after invasive procedures. Clinical trials and management studies in recent years have helped inform our approach to these patients, but much of the guidance is still based on expert consensus.

Recurrent migration of peripherally inserted central catheter into the azygos vein.

Peripherally inserted central catheter (PICC) migration into azygos vein (AV) is a rare complication. It is recognised only when catheter malfunction occurs or when patients develop associated complications. PICC migration into AV has been reported to be associated with various complications such as catheter malfunction, perforation, haemorrhage, thrombosis, infection and stenosis of AV. Pleural effusion and trachea-azygos fistulas have also been reported. We present a patient with recurrent migration of PICC into AV after an initial corrective repositioning during the same hospital stay. In this case, PICC migration was possibly related to left-sided approach, use of smaller diameter PICC, severe congestive heart failure and her bedbound status. PICC migration should be considered when PICC found be malfunctioning, especially if associated with the above risk factors.

Letter to the Editor, What Can Be Done to Maintain Positive Patient Experience and Improve Residents' Satisfaction? In Reference to: "Standardized Attending Rounds to Improve the Patient Experience: A Pragmatic Cluster Randomized Controlled Trial".

We read the article by Monash et al. published in the March 2017 issue with great interest. This randomized study showed a discrepancy between patients' and residents' satisfaction with standardized rounds; for example, residents reported less autonomy, efficiency, teaching, and longer time of rounds.

The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions.

Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to be beneficial in the management of a patient with the above-mentioned toxidromes. However, most of the available evidence originates from case reports, case series, and expert consensus recommendations. The potential mechanisms of sodium bicarbonate include high sodium load and the development of metabolic alkalosis with resultant decreased tissue penetration of the toxic substance with subsequent increased urinary excretion. While receiving sodium bicarbonate, patients must be monitored for the development of associated side effects including electrolyte abnormalities, the progression of metabolic alkalosis, volume overload, worsening respiratory status, and/or worsening metabolic acidosis. Patients with oliguric/anuric renal failure and advanced decompensated heart failure should not receive sodium bicarbonate.

Procarbazine, lomustine and vincristine for recurrent high-grade glioma.

BACKGROUND: Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine, lomustine (CCNU) and vincristine - is one of the treatment options at recurrence. There has been no meta-analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG. OBJECTIVES: To assess the effectiveness and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy with other interventions in adults with recurrent high-grade glioma. To investigate whether predefined subgroups of people benefit more or less from chemotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2017), MEDLINE (1946 to 22 May 2017), and Embase (1980 to 22 May 2017). We searched trial registries including the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch) and the National Institutes of Health (NIH; ClinicalTrials.gov). We searched the reference lists of all identified studies; the electronic table of contents of the Journal of Neuro-Oncology (1983 to 2016) and Neuro-Oncology (1999 to 2016); and conference abstracts from the Society for Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO 2004 to 2016). We also searched unpublished grey literature and other regional databases. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) where PCV was used to treat adults with recurrent HGG. Comparison arm included no chemotherapy, other second line chemotherapy or best supportive care. DATA COLLECTION AND ANALYSIS: Two review authors extracted the data and undertook a 'Risk of bias' assessment and critical appraisal of the studies. MAIN RESULTS: We identified two RCTs meeting our inclusion criteria. The two trials tested different comparisons.One RCT included 35 participants and compared PCV with 'eight drugs in one day' multidrug chemotherapy, which is a combination of drugs with different mechanisms of action. Median survival was 6 months for the PCV group and 6.5 months for the 'eight drugs in one day' group. Adverse event outcomes were not graded or quantified. Progression-free survival (PFS) and quality of life (QoL) were not described in the methods and were not an outcome of interest. The sample size in this study was small, which lead to insufficient statistical power to detect clinical differences. According to the GRADE approach we judged the quality of evidence to be low for survival outcome and very low for chemotherapy toxicityThe second multi-institutional RCT included 447 participants and compared PCV with Temozolomide (TMZ). Participants were randomised into three arms to receive PCV, and two different regimens of TMZ in a 2:1:1 ratio at first recurrence. The trial reported a median overall survival of 6.7 months and 7.2 months for the PCV and TMZ group respectively. It reported a PFS of 3.6 months for the PCV group and 4.7 months for the TMZ group. There was no observed difference of effect on overall survival (hazard ratio (HR) 0.91, 95% CI 0.74 to 1.11; P = 0.35) or PFS (HR 0.89, 95% CI 0.73 to 1.08; P = 0.23) in participants receiving PCV or TMZ chemotherapy. The proportion of people with at least one grade 3 or 4 adverse event was not clinically important at 9.2% versus 12.2% in PCV and TMZ arms respectively. Mean QoL scores calculated at baseline, 12 weeks and 24 weeks was 51.9 versus 59.8 favouring TMZ (P = 0.04) which is statistically but not clinically significant and was less than the pre-defined 10 point change for moderate improvement. We judged the GRADE quality of evidence to be moderate for overall survival, PFS, and chemotherapy toxicity and low for QoL. AUTHORS' CONCLUSIONS: Evidence is based on a single large trial analysis as the other trial was small, with inadequate power to detect survival difference. Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes. Adverse events are similar and QoL scores are statistically but not clinically significant between TMZ and PCV. Further RCTs should be conducted with adequate power following CONSORT guidelines with emphasis on QoL outcomes.

Rare case of losartan-induced cough complicated by rectus sheath haematoma: in a patient on rivaroxaban therapy.

Spontaneous rectus sheath haematomas and cough secondary to losartan are individually rare conditions. Abdominal wall haematomas present with abdominal pain and abdominal mass. Most patients are managed conservatively; Surgery or embolisation is indicated for shock, infection, rupture into the peritoneum or intractable pain. This is a man aged 65 years presented with dry cough and right-sided abdominal pain. He started losartan a few weeks prior to the onset of cough and had been on rivaroxaban for prior deep venous thrombosis. The right side of his abdomen was distended, bruised and tender. His haemoglobin dropped from 13.3to 9.5 g/dL. CT abdomen/pelvis showed a large 14.5×9.1×4.5 cm haematoma within the right lateral rectus muscle. His only risk factor for developing rectus sheath haematoma was cough in the setting of anticoagulation. Dry cough due to angiotensin receptor blockers is rare, but can have very serious consequences.

A randomized controlled prospective study comparing a low dose bupivacaine and fentanyl mixture to a conventional dose of hyperbaric bupivacaine for cesarean section.

CONTEXT: Hormonal and mechanical factors make obstetric patients need strict dose calculations of local anesthetics intrathecally for spinal anesthesia. Any greater dose of local anesthetics can cause hemodynamic instability, maternal morbidity and any lesser dose can produce inadequate block. Hence, we hypothesized in our study that by using low dose of bupivacaine with fentanyl can maintain stable hemodynamics and provide better analgesia. AIM: The aim was to compare the hemodynamics and duration of analgesia using a low dose (7.5 mg) bupivacaine fentanyl mixture to a conventional dose (10 mg) of hyperbaric bupivacaine for cesarean section. SETTINGS AND DESIGN: Double-blinded, randomized, controlled prospective study was conducted at a tertiary academic hospital from 2008 to 2011. MATERIALS AND METHODS: Fifty singleton parturient, scheduled for elective caesarean section were randomly allocated into two groups. Study group (group-S) received a combination of 25 µg fentanyl and 7.5 mg of hyperbaric bupivacaine, whereas the control group (group-C) received 10 mg of hyperbaric bupivacaine. Maternal hemodynamics, sensory and motor block, duration of analgesia and the Apgar score of the newborn were compared between the groups. STATISTICAL ANALYSIS USED: Observational descriptive statistics, statistical package for social sciences (SPSS Inc. Released 2006, SPSS for Windows, Version 15.0. Chicago), paired t-test was used as applicable. RESULTS: The blood pressure significantly decreased with >25% fall from the baseline in group-C (98.76 ± 8.36) than in group-S (117.32 ± 12.21) with P < 0.001. The duration of effective analgesia was significantly prolonged in the study group than in the control group (P < 0.001). CONCLUSION: The combination of low dose bupivacaine and fentanyl in comparison to bupivacaine alone is hemodynamically stable and prolonged duration of analgesia in caesarean section.

Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.

BACKGROUND: The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. OBJECTIVES: To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. METHOD: Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. RESULTS: Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. CONCLUSIONS: No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients.