All day long. Interview by Carol Davis

Hyperemess, severe and excessive vomiting during pregnancy, is a distressing condition that can require hospital treatment. One hospital has set up a dedicated, midwife-led day unit for these women.     

Kidney failure,CKD progression and mortality after nephrectomy

Purpose

This study tested the hypothesis that progression of chronic kidney disease (CKD) is less aggressive in patients whose primary cause of CKD was nephrectomy, compared with non-surgical causes.

Methods

A sample of 5983 patients from five specialist nephrology practices was ascertained from the Queensland CKD Registry. Rates of kidney failure/death were compared on primary aetiology of CKD using multivariable Cox proportional hazards models. CKD progression was compared using multivariable linear and logistic regression analyses.

Results

Of 235 patients with an acquired single kidney as their primary cause of CKD, 24 (10%) and 38 (17%) developed kidney failure or died at median [IQR] follow-up times of 12.9 [2.5–31.0] and 33.6 [18.0–57.9] months after recruitment. Among patients with an eGFR?<?45 mL/min per 1.73m² at recruitment, patients with diabetic nephropathy and PCKD had the highest rates (per 1000 person-years) of kidney failure (107.8, 95% CI 71.0–163.8; 75.5, 95% CI 65.6–87.1); whereas, patients with glomerulonephritis and an acquired single kidney had lower rates (52.9, 95% CI 38.8–72.1; 34.6, 95% CI 20.5–58.4, respectively). Among patients with an eGFR?≥?45 mL/min per 1.73m², those with diabetic nephropathy had the highest rates of kidney failure (16.6, 95% CI 92.5–117.3); whereas, those with glomerulonephritis, PCKD and acquired single kidney had a lower risk (11.3, 95% CI 7.1–17.9; 11.7, 95% CI 3.8–36.2; 10.7, 95% CI 4.0–28.4, respectively).

Conclusion

Patients who developed CKD after nephrectomy had similar rates of adverse events to most other causes of CKD, except for diabetic nephropathy which was consistently associated with worse outcomes. While CKD after nephrectomy is not the most aggressive cause of kidney disease, it is by no means benign, and is associated with a tangible risk of kidney failure and death, which is comparable to other major causes of CKD.

     

The relationship of three-dimensional joint space width on weight-bearing CT with pain and physical function

Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. Three-dimensional (3D) joint space width (JSW), measured from weight-bearing computed tomography (CT) images, may yield a more accurate correlation with patients’ symptoms. We assessed the cross-sectional association between 3D JSW and self-reported pain and physical function. Five hundred twenty eight knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight-bearing CT scanner was used to acquire bilateral, weight-bearing, fixed-flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and JSW was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with JSW less than 2.0 and 2.5 mm, respectively, were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with JSW less than 2.0 mm (P = .07 for the highest vs the lowest tertile). Participants who reported greater functional limitations had a greater joint area with JSW less than 2.0 mm (P = .02 for the highest vs the lowest tertile). There appears to be an association between the medial tibiofemoral area with JSW less than 2.0 mm and pain and physical function.     

Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder

The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and both NR3C1 and FKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for FKBP5 and NR3C1 in risk for PTSD. Overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of PTSD.     

Amikacin population pharmacokinetics among paediatric burn patients

Introduction

The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.

Methods

Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10–20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.

Results

The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean C_max was 33.2 ± 9.4 μg/mL and the mean C_min was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97–6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0–19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0–80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44–4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.

Discussion

Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.     

Developing a culture of nursing research through clinical-academic partnership

Evidence based practice is essential to advanced practice nursing, enabling the delivery of quality care and improved patient outcomes. As the name suggests, it requires healthcare decisions to be based on the best available and current evidence. Advanced practice nurses need astute critical analysis skills to appraise the evolving literature, and require research skills to lead on scientific inquiry and develop the profession. Yet, advanced practice nurses may not recognize themselves as research leaders. Participation in a journal club can promote evidence-based practice, improve clinician's critical thinking skills, and expose members to different research methodologies, however, nurses continue to face barriers to participation in these clubs. Establishing a clinical-academic partnership appears to be both mutually beneficial for clinicians and academics and is a significant enabler in the sustainability and functioning of the club through sharing expertise and experience. A supportive workplace culture is favourable to research utilization and knowledge translation. This paper outlines the role, practicalities, challenges, and benefits of setting up a hybrid urology journal and research club for advanced practice nurses in a clinical-academic partnership.     

Malignant tumours of the small intestine

Adenocarcinoma, neuroendocrine tumours, sarcomas and lymphomas are the four most common malignant tumours arising in the small intestine, although over forty different histological subtypes are described. Collectively these account for only 2% of cancers of the digestive system. The incidence of small bowel cancer has increased in recent decades with a four-fold increase in carcinoid tumours. Risk factors for small bowel tumours include coeliac disease, inflammatory bowel disease and a number of genetic abnormalities. The non-specific nature of their symptoms and the difficulty in visualising these tumours with normal endoscopic techniques often results in late diagnosis. Furthermore the paucity of literature on this topic has made it difficult to standardise management. There has however been marked improvement in imaging methods resulting in earlier diagnosis in many cases. As expected, early detection of localised, well differentiated tumours followed by surgical resection with negative margins offers the best chance of long term survival. Better adjuvant treatment, notably for gastrointestinal stromal tumours, has improved 5-year survival rates significantly. Development of surveillance guidelines for at risk populations may be a valuable way of improving early diagnosis of this challenging group of conditions.