A pilot randomised controlled comparison of continuous veno–venous haemofiltration and extended daily dialysis with filtration: effect on small solutes and acid–base balance

Background and aims Continuous veno–venous haemofiltration (CVVH) is an established treatment for acute renal failure (ARF). Recently, extended intermittent dialytic techniques have been proposed for the treatment of ARF. The aim of this study was to compare these two approaches. Setting Intensive care unit of tertiary hospital. Subjects Sixteen critically ill patients with ARF. Design Randomised controlled trial. Intervention We randomised sixteen patients to three consecutive days of treatment with either CVVH (8) or extended daily dialysis with filtration (EDDf) (8) and compared small-solute, electrolyte and acid–base control. Results There was no significant difference between the two therapies for urea or creatinine levels over 3 days. Of 80 electrolyte measurements taken before treatment, 19 were abnormal. All values were corrected as a result of treatment, except for one patient in the CVVH group who developed hypophosphataemia (0.54 mmol/l) at 72 h. After 3 days of treatment, there was a mild but persistent metabolic acidosis in the EDDf group compared to the CVVH group (median bicarbonate: 20 mmol/l vs. 29 mmol/l: p = 0.039; median base deficit: –4 mEq/l vs. –2.1 mEq/l, p = 0.033). Conclusions CVVH and EDDf as prescribed achieved similar control of urea, creatinine and electrolytes. Acidosis was better controlled with CVVH. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Clinical application and viability of cryopreserved cadaveric skin allografts in severe burn: A retrospective analysis

Introduction

Cadaveric cutaneous allografts are used in burns surgery both as a temporary bio-dressing and occasionally as definitive management of partial thickness burns. Nonetheless, limitations in the understanding of the biology of these grafts have meant that their role in burns surgery continues to be controversial.

Methods

A review of all patients suffering 20% or greater total body surface area (TBSA) burns over an eight year period that received cadaveric allografts were identified. To investigate whether tissue viability plays a role in engraftment success, five samples of cryopreserved cadaveric cutaneous allograft processed at the Donor Tissue Bank of Victoria (DTBV) were submitted to our laboratory for viability analysis using two methods of Trypan Blue Exclusion and tetrazolium salt (MTT) assays.

Results

During the study period, 36 patients received cadaveric allograft at our institution. The average total burn surface area (TBSA) for this group of patients was 40% and all patients received cadaveric skin as a temporizing measure prior to definitive grafting. Cadaveric allograft was used in complicated cases such as wound contamination, where synthetic dressings had failed. Viability tests showed fewer than 30% viability in processed allografts when compared to fresh skin following the thawing process. However, the skin structure in the frozen allografts was histologically well preserved.

Conclusion

Cryopreserved cutaneous cadaveric allograft has a positive and definite role as an adjunct to conventional dressing and grafting where available, particularly in patients with large TBSA burns. The low viability of cryopreserved specimens processed at DTBV suggests that cell viability in cadaveric allograft may not be essential for its clinical function as a wound dressing or even as permanent dermal substitute.     

Incidence of non-candidal fungal infections in severe burn injury: An Australian perspective

Introduction

Infection remains the primary cause of morbidity and mortality in the burns patient population. While candidal infection in burns patients is well described, there is dearth of information regarding non-candidal fungal infections in this setting.

Method

All adult burns patients who developed non-candidal fungal infections over a period of 10 years (between January 2001 and June 2011) were included. Retrospective data analyzed included patient demographics, organisms cultured, antibiotic susceptibility patterns, treatment, length of stay and overall mortality.

Results

The incidence of non-candidal fungal infections at our centre over the time period studied was 0.04%. A total of 12 patients had a fungus other than Candida isolated. Of these 12 patients, seven were thought to have clinically significant fungal infections and were treated with targeted anti-fungal therapy. Between them, seven species of fungus were isolated: Aspergillus fumigatus (n = 7), Scedosporium prolificans (n = 2), Fusarium solani (n = 2), Mucor spp. (n = 2), Absydia corymbifera (n = 1), Penicillium (n = 1) and Alternaria spp. (n = 1). Of those definitively treated, two died, although fungal infection was not believed to be a contributing factor to these deaths.

Conclusion

We demonstrate a low incidence and attributable mortality of non-candidal fungal infections in the setting of early antifungal therapy and extensive surgical debridement at our state-wide Burns Service.     

Engaging Patients with Digital Tools: What We Think We Know

Patients who are engaged in their own care have better outcomes and cost the health care system less money. Creating the environment that supports patient engagement has been a recent focus across the United States, and digital tools have been suggested as an important piece of patient engagement. We discuss what we think we know about digital engagement, and present data of what is actually occurring.There’s no shortage of activity within the health information technology (HIT) space. Although our positions within a university afford us the opportunity to pick and choose when and how we will engage in the advancements that are rapidly confronting US hospitals and health systems, we anticipate that many of Hospital Pharmacy’s readers do not have that opportunity. From our e-mail exchanges with you and from talking with you at conferences, it’s clear that many of you face situations in which top-down decisions directly impact what your pharmacy department does as it relates to HIT. We focus this column on bringing you relevant HIT-related information.By the time you are reading this, the ALS Ice Bucket Challenge is likely to have given way to the next social media craze. But we believe that the Ice Bucket Challenge has implications that apply to the challenges and opportunities you face in your hospital setting. If you are not familiar with the Ice Bucket Challenge, take a few moments to search for it in your favorite browser. The challenge shows how social media, specifically social networks like Facebook, can provide a medium for rapid transmission of information; depending on the topic, the outcome of this rapid spread of information can have a significant impact. By the end of August 2014, the ALS Association received nearly $80 million in donations compared to $2.5 million for the same time frame in 2013.The use of Web 2.0 tools like social networks for health-related reasons is called Health 2.0. We have advocated that hospitals and health systems begin using Health 2.0 tools to engage their patients. Patient portals are a type of Health 2.0 tool that many hospitals have implemented to engage their patients. Portals are dynamic, collaborative, allow the access and management of information (by the patient or caregiver), and are largely patient-centric. Are all of your patients using your portal? Most likely they are not. Does that mean that no patients will use your portal? Also, most likely not. What about other Health 2.0 tools and emerging technologies that you are facing in your practice?We can draw on existing data to gain insight into what engagement you can likely expect from your patients. Biesdorf and Niedermann published a list of myths related to the use of Internet-based technologies and other emerging technologies for health-related reasons.¹ Susannah Fox provided her perspective on the myths, including specific data to support her argument that the myths are not true.² We will use these myths and Fox’s data to structure our presentation of data that we believe should be brought into discussion as your institution considers its plan for engaging patients.Myth 1: People don’t want to use digital services for health care. The Pew Internet Project (www.pewinternet.org) provides numerous examples that refute this myth. For example, 87% of American adults use the Internet, 70% of American adults have high-speed access at home, and, most notably, 72% of American adults have looked for health information online. Nearly 50% of adults look online for information for someone else. These “caregivers,” as they are called, are more likely to engage in online health activities like participating in support groups and contacting their providers.Myth 2: Only young people want to use digital services. The “older crowd” can be slower to adopt new digital tools, but this does not apply to all tools. For example, 87% of American adults are online. Among those 50 to 64 years of age, 88% are online. The percentage drops to 57% when we look at those 65 and older. Although there is less online participation in the oldest segment of the population, we are still looking at nearly 6 in 10 adults. Certainly, it’s not just the younger crowd using online tools.Myth 3: Mobile health is the game changer. This myth may seem to contradict previous articles we have written describing the potential value in mobile devices as tools to gather, analyze, and share health-related information, including information that the patient manages. Our rule of thumb with mobile is the same as with any technology – you must know your audience. Eighty percent of people with 2 or more chronic conditions track a health indicator. However, only 4% use an app to do so. We believe that patients’ use of apps is influenced by many factors, including general comfort with the device, concerns over security and privacy, lack of encouragement to use apps by trusted individuals (ie, providers), and a general wait-and-see attitude. We do believe mobile will profoundly change health care, but it is not there yet.Myth 4: Patients want innovative features and apps. For those adults who track health indicators, 49% keep track in their heads, 34% use paper records, and 21% use some form of technology. The message is clear that knowing who you serve and what fits their daily routine (as well as their comfort level) is paramount in designing tools to engage your patients.Myth 5: A comprehensive platform of services is a prerequisite for creating value. As your institution starts to digitally engage patients, it will be easy to identify a wide range of tools for immediate implementation based on the expectation that “if you build it, they will come.” We believe a systematic approach to selection and implementation is best. The process should be guided by direct input from the target users (ie, patients) in terms of what tools they believe they will use. Existing data and reports suggest that patients prefer portal-based communication tools like secure messaging over apps.In discussing the myths above, we have not touched on the pharmacist’s role in these activities. We believe that pharmacy should be involved in any discussions of technologies or tools that touch the medication use process at any time in the patient’s interaction with the health system, whether that is an acute stay, an outpatient experience, or an ambulatory clinic setting. We welcome your questions and comments about the work you have before you or the work you have completed related to engaging patients with digital tools (Brent at ude.nrubua@nerbxof and Bill at ude.nrubua@gbeklef).     

Population pharmacokinetic analysis of axitinib in healthy volunteers

AIMS

Axitinib is a potent and selective second generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 approved for second line treatment of advanced renal cell carcinoma. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in axitinib disposition following single dose administration in healthy volunteers.

METHODS

Plasma concentration–time data from 337 healthy volunteers in 10 phase I studies were analyzed, using non-linear mixed effects modelling (nonmem) to estimate population pharmacokinetic parameters and evaluate relationships between parameters and food, formulation, demographic factors, measures of renal and hepatic function and metabolic genotypes (UGT1A1*28 and CYP2C19).

RESULTS

A two compartment structural model with first order absorption and lag time best described axitinib pharmacokinetics. Population estimates for systemic clearance (CL), central volume of distribution (V_c), absorption rate constant (k_a) and absolute bioavailability (F) were 17.0 l h⁻¹, 45.3 l, 0.523 h⁻¹ and 46.5%, respectively. With axitinib Form IV, k_a and F increased in the fasted state by 207% and 33.8%, respectively. For Form XLI (marketed formulation), F was 15% lower compared with Form IV. CL was not significantly influenced by any of the covariates studied. Body weight significantly affected V_c, but the effect was within the estimated interindividual variability for V_c.

CONCLUSIONS

The analysis established a model that adequately characterizes axitinib pharmacokinetics in healthy volunteers. V_c was found to increase with body weight. However, no change in plasma exposures is expected with change in body weight; hence no dose adjustment is warranted.     

The interaction of sex,height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual‐patient data meta‐analysis

Aims

To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women.

Methods and results

In an individual‐patient data meta‐analysis of five randomized controlled trials, all‐cause mortality and the composite of all‐cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end‐diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all‐cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women.

Conclusions

In this individual‐patient data meta‐analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. ( ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

     

An analysis of T-cell receptor variable region gene expression in major histocompatibility complex disparate mice.

To define the impact of major histocompatibility complex (MHC)-encoded glycoproteins on the selection of the T-cell receptor repertoire, we have determined the frequency with which T-cell receptor variable region (V alpha and V beta) genes are expressed in T cells from MHC disparate mice. Approximately 500 T-cell hybridomas were generated from each of three strains of MHC congenic mice [B10 (H-2b), B10.BR (H-2k), and B10.Q (H-2q)] by fusing mitogen-stimulated lymph node T cells with the thymoma BW5147. RNA was prepared from 1629 individual hybridomas and analyzed for the expression of 10 V alpha and 16 V beta gene families. These experiments reveal significant differences in the relative contributions of 1 V alpha gene family (V alpha 3) and several V beta gene segments (V beta 5.1, -5.2, -11, and -12) to the T-cell receptor repertoire of MHC disparate mice.     

Do discharge codes underestimate hospitalisation due to heart failure? Validation study of hospital discharge coding for heart failure

BACKGROUND: Discharge codes are frequently used to describe hospital activity related to heart failure (HF). OBJECTIVES: To determine whether discharge codes for HF underestimated or overestimated hospital activity related to HF. DESIGN: Patients with atrial fibrillation (AF), who commonly have HF, were identified and their case notes reviewed to identify cases of HF missed by discharge codes. PARTICIPANTS AND METHODS: Patients admitted between November 1997 and January 1998 with either HF or AF. Identification of HF and AF by ICD10 hospital discharge codes. Identification of additional cases of AF from a central hospital-wide ECG database. RESULTS: We identified 330 cases with an ICD 10 code for HF, of which 43 (13%) were deemed to be miscoded, 32 patients (10%) were classified as possible, 39 (12%) as probable and 216 (65%) as definite HF. Results were similar whether or not HF was the primary discharge diagnosis. We identified 452 patients with AF, of whom 45 (10%) were classified as probable and 193 (43%) as definite HF. 129 (54%) of these cases had no diagnostic discharge code for HF. ICD 10 discharge codes for HF were correct in 77% of cases but identified only 66% of patients with probable or definite HF in this analysis. Screening of other diagnoses would have identified further cases of HF. CONCLUSIONS: Hospital discharge codes substantially underestimate hospital events related to HF in the UK.