Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.     

In vitro and in vivo mammalian mutation assays support a nonmutagenic mechanism of carcinogenicity for hydrazine

Hydrazine has been described as a mutagenic, probable human carcinogen. It is mutagenic in in vitro systems such as bacterial reverse mutation (Ames) tests and some yeast systems, as well as in in vivo systems with drosophila. It was shown to cause chromosome damage both in vitro and in vivo but was negative in some well‐validated mammalian mutation systems such as CHO HPRT assays. Importantly, there is only one in vivo gene mutation test reported, which was negative. Our objective was to determine if hydrazine is mutagenic in mammalian test systems. Thus, we conducted an in vitro gene mutation test in Muta?Mouse lung epithelial cells (FE1 cell assay) and a regulatory‐compliant in vivo Big Blue® mouse test. Consistent with previous reports, an additional six‐well Ames assay showed that hydrazine was mutagenic to bacteria. The FE1 cell assay was negative in conditions with and without metabolic activation when tested to cytotoxicity limits. In the Big Blue® mouse study, female mice received dosages of hydrazine up to 10.9 mg/kg via drinking water for 28 days. This dose is comparable to a dose used in a carcinogenicity study where female mice had significant increases in hepatocellular adenoma at 11.5 mg/kg. There were no increases in mutant frequency in liver and lung, two tissues sensitive to the carcinogenic effects of hydrazine in mice. Our research shows that hydrazine is not mutagenic in mammalian cells either in vitro or in vivo, indicating mutagenicity may not play a role in the carcinogenicity of hydrazine.     

A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.     

Effect of a clinical decision support system on adherence to a lower tidal volume mechanical ventilation strategy

Purpose

The purpose of the study was to measure the effect of a computerized decision support system (CDSS) on adherence to tidal volume (V_T) recommendations.

Materials and Methods

We performed a prospective before-after evaluation study on applied V_T to examine the impact of a CDSS on adherence to our local protocol in a 30-bed mixed medical-surgical intensive care unit of a university hospital. All intensive care unit patients who were intubated and mechanically ventilated for at least 1 hour were included.

Results

A total of 3 663 674 V_T records of 696 patients were analyzed. The average volume greater than 6 mL/kg predicted body weight (PBW) and the mean percentage of ventilation time with V_T greater than 6 mL/kg PBW decreased after intervention by 6.0% and 3.4%, respectively (not significant). A stronger effect of the decision support intervention was found among patients with longer duration of mechanical ventilation (>24 hours): for these patients, the average V_T in exceeding 6 mL/kg PBW and the mean percentage of ventilation time with V_T greater than 6 mL/kg PBW decreased after intervention by 18.3% (P = .01) and 9.5% (P = .01), respectively. In this group, the mean percentage of ventilation time with V_T records between 8 and 10, between 10 and 12, and greater than 12 mL/kg PBW decreased by 21.8% (P = .006), 21.5% (P = .047), and 24.7% (P = .155), respectively.

Conclusions

The use of a CDSS, integrated in a patient data management system, improves implementation of a lower V_T mechanical ventilation strategy for patients ventilated for longer than 24 hours.     

West Nile Virus Infection Incidence Based on Donated Blood Samples and Neuroinvasive Disease Reports,Northern Texas,USA, 2012

During the 2012 outbreak of West Nile virus in the United States, approximately one third of the cases were in Texas. Of those, about half occurred in northern Texas. Models based on infected blood donors and persons with neuroinvasive disease showed, respectively, that ≈0.72% and 1.98% of persons in northern Texas became infected.     

Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses

We performed a comparison between Neuropathy Impairment Scale‐sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS‐motor vs. the Medical Research Council sum score in patients with Guillain‐Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance‐related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch‐transformed (RT)‐intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2–4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM‐MGUSP: 23) were serially examined with 12 months follow‐up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT‐mISS compared to RT‐NISs. Responsiveness was equal for the RT‐motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow‐up in the latter group of patients.     

Facilitators and barriers to implementing pharmacist-prescribed hormonal contraception in California independent pharmacies

ABSTRACT

In 2013, California passed legislation to expand the scope of pharmacist practice, including authorizing pharmacists to prescribe hormonal contraception. Pharmacist-prescribed contraception was largely unavailable across the state in 2017. This study aimed to identify barriers and facilitators to offering this service in California independent pharmacies. To do so, we thematically analyzed qualitative data from structured interviews with 36 pharmacists working in independent pharmacies in 2016–17. We found that pharmacists anticipated general benefits from expanding their roles to prescribe contraception, including increasing health care access and decreasing costs. In contrast, described barriers were concrete, including lack of financial incentives and business risks for independent pharmacies. Specific barriers to prescribing hormonal contraception included time required to screen and counsel women about contraception and concerns that pharmacist-prescribed contraception would increase liability and lead to patients seeking health care less frequently. This study suggests that incentives and barriers identified by the respondents are likely to have varied and unequal impacts, with immediate barriers being potentially prohibitive for pharmacists to prescribe contraception. For independent pharmacies, perceived business risks and lack of insurance reimbursement may outweigh professional support for prescribing contraception, limiting the public health impact of legislation that should increase contraceptive access.