Paul Snelling

Endemic Melioidosis in Tropical Northern Australia: A 10-Year Prospective Study and Review of the Literature

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

The views of patients and carers in treatment decision making for chronic kidney disease: systematic review and thematic synthesis of qualitative studies.

Objective To synthesise the views of patients and carers in decision making regarding treatment for chronic kidney disease, and to determine which factors influence those decisions. Design Systematic review of qualitative studies of decision making and choice for dialysis, transplantation, or palliative care, and thematic synthesis of qualitative studies. Data sources Medline, PsycINFO, CINAHL, Embase, social work abstracts, and digital theses (database inception to week 3 October 2008) to identify literature using qualitative methods (focus groups, interviews, or case studies). Review methods Thematic synthesis involved line by line coding of the findings of the primary studies and development of descriptive and analytical themes. Results 18 studies that reported the experiences of 375 patients and 87 carers were included. 14 studies focused on preferences for dialysis modality, three on transplantation, and one on palliative management. Four major themes were identified as being central to treatment choices: confronting mortality (choosing life or death, being a burden, living in limbo), lack of choice (medical decision, lack of information, constraints on resources), gaining knowledge of options (peer influence, timing of information), and weighing alternatives (maintaining lifestyle, family influences, maintaining the status quo). Conclusions The experiences of other patients greatly influenced the decision making of patients and carers. The problematic timing of information about treatment options and synchronous creation of vascular access seemed to predetermine haemodialysis and inhibit choice of other treatments, including palliative care. A preference to maintain the status quo may explain why patients often remain on their initial therapy.

The epidemiology of melioidosis in Australia and Papua New Guinea.

Melioidosis was first described in Australia in an outbreak in sheep in 1949 in north Queensland (22 degrees S). Human melioidosis was first described from Townsville (19 degrees S) in 1950. Melioidosis is hyperendemic in the Top End of the Northern Territory (NT) and as in parts of northeastern Thailand it is the commonest cause of fatal community-acquired septicemic pneumonia. In the 9 years since 1989 the prospective NT melioidosis study at Royal Darwin Hospital (12 degrees S) has documented 206 culture confirmed cases of melioidosis, with an average annual incidence of 16.5/100,000. Melioidosis is also seen in the north of Western Australia and north Queensland, including the Torres Strait Islands, but is uncommon in adjacent Papua New Guinea. Serological studies suggest that infection is rare in the Port Moresby region, but there is emerging evidence of melioidosis from Western Province. The NT study has documented inoculating events in 52 (25%) of cases, with an incubation period of 1-21 days (mean 9 days); 84% of cases had acute disease from presumed recent acquisition and 13% had chronic disease (sick, > 2 months). In 4% there was evidence of possible reactivation from a latent focus; 28 of 153 (18%) males had prostatic abscesses. The overall mortality was 21% (43 cases), with a mortality rate in septicemic cases (95) of 39% and in non-septicemic cases (103) of 4%. Pneumonia was the commonest presentation in both groups and, in addition, eight patients (two deaths) presented with melioidosis encephalomyelitis. Melioidosis clusters in temperate Australia are attributed to animals imported from the north. Molecular typing of Burkholderia pseudomallei isolates from temperate southwest Western Australia showed clonality over 25 years. In this outbreak and in studies from the NT, some soil isolates are molecularly identical to epidemiologically related animal and human isolates. Molecular typing has implicated the water supply in two clonal outbreaks in remote aboriginal communities in northern Australia. Further prospective collaborative studies are required to evaluate whether there are truly regional differences in clinical features of melioidosis and to better understand how B. pseudomallei is acquired from the environment.

Factors influencing patient choice of dialysis versus conservative care to treat end-stage kidney disease

Background: For every patient with chronic kidney disease who undergoes renal-replacement therapy, there is one patient who undergoes conservative management of their disease. We aimed to determine the most important characteristics of dialysis and the trade-offs patients were willing to make in choosing dialysis instead of conservative care. Methods: We conducted a discrete choice experiment involving adults with stage 3–5 chronic kidney disease from eight renal clinics in Australia. We assessed the influence of treatment characteristics (life expectancy, number of visits to the hospital per week, ability to travel, time spent undergoing dialysis [i.e., time spent attached to a dialysis machine per treatment, measured in hours], time of day at which treatment occurred, availability of subsidized transport and flexibility of the treatment schedule) on patients’ preferences for dialysis versus conservative care. Results: Of 151 patients invited to participate, 105 completed our survey. Patients were more likely to choose dialysis than conservative care if dialysis involved an increased average life expectancy (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.57–2.15), if they were able to dialyse during the day or evening rather than during the day only (OR 8.95, 95% CI 4.46–17.97), and if subsidized transport was available (OR 1.55, 95% CI 1.24–1.95). Patients were less likely to choose dialysis over conservative care if an increase in the number of visits to hospital was required (OR 0.70, 95% CI 0.56–0.88) and if there were more restrictions on their ability to travel (OR = 0.47, 95%CI 0.36–0.61). Patients were willing to forgo 7 months of life expectancy to reduce the number of required visits to hospital and 15 months of life expectancy to increase their ability to travel. Interpretation: Patients approaching end-stage kidney disease are willing to trade considerable life expectancy to reduce the burden and restrictions imposed by dialysis.

Exploring the Pathways Leading from Disadvantage to End-Stage Renal Disease for Indigenous Australians

Indigenous Australians are disadvantaged, relative to other Australians, over a range of socio-economic and health measures. The age- and sex-adjusted incidence of end-stage renal disease (ESRD)--the irreversible preterminal phase of chronic renal failure--is almost nine times higher amongst Indigenous than it is amongst non-indigenous Australians. A striking gradient exists from urban to remote regions, where the standardised ESRD incidence is from 20 to more than 30 times the national incidence. We discuss the profound impact of renal disease on Indigenous Australians and their communities. We explore the linkages between disadvantage, often accompanied by geographic isolation, and both the initiation of renal disease, and its progression to ESRD. Purported explanations for the excess burden of renal disease in indigenous populations can be categorised as: primary renal disease explanations;genetic explanations;early development explanations; and socio-economic explanations. We discuss the strengths and weaknesses of these explanations and suggest a new hypothesis which integrates the existing evidence. We use this hypothesis to illuminate the pathways between disadvantage and the human biological processes which culminate in ESRD, and to propose prevention strategies across the life-course of Indigenous Australians to reduce their ESRD risk. Our hypothesis is likely to be relevant to an understanding of patterns of renal disease in other high-risk populations, particularly indigenous people in the developed world and people in developing countries. Furthermore, analogous pathways might be relevant to other chronic diseases, such as diabetes and cardiovascular disease. If we are able to confirm the various pathways from disadvantage to human biology, we will be better placed to advocate evidence-based interventions, both within and beyond the scope of the health-care system, to address the excess burden of renal and other chronic diseases among affected populations.

Dialysis modality preference of patients with CKD and family caregivers: a discrete-choice study

BACKGROUND Dialysis modality preferences of patients with chronic kidney disease (CKD) and family caregivers are important, yet rarely quantified. STUDY DESIGN Prospective, unlabeled, discrete-choice experiment with random-parameter logit analysis. SETTING & PARTICIPANTS Adults with stages 3-5 CKD and caregivers educated about dialysis treatment options from 8 Australian renal clinics. PREDICTORS Preferences for and trade-offs between the dialysis treatment attributes of life expectancy, number of hospital visits per week, ability to travel, hours per treatment, treatment time of day, subsidized transport service, and flexibility of treatment schedule. OUTCOMES & MEASUREMENTS Results presented as ORs for preferring home-based or in-center dialysis to conservative care. RESULTS 105 predialysis patients and 73 family caregivers completed the study. Median patient age was 63 years, and mean estimated glomerular filtration rate was 18.1 (range, 6-34) mL/min/1.73 m(2). Median caregiver age was 61 years. Home-based dialysis (either peritoneal or home hemodialysis) was chosen by patients in 65% of choice sets; in-center dialysis, in 35%; and conservative care, in 10%. For caregivers, this was 72%, 25%, and 3%, respectively. Both patients and caregivers preferred longer rather than shorter hours of dialysis (ORs of 2.02 [95% CI, 1.51-2.70] and 2.67 [95% CI, 1.85-3.85] for patients and caregivers, respectively), but were less likely to choose nocturnal than daytime dialysis (ORs of 0.07 [95% CI, 0.01-0.75] and 0.03 [95% CI, 0.01-0.20]). Patients were willing to forgo 23 (95% CI, 19-27) months of life expectancy with home-based dialysis to decrease their travel restrictions. For caregivers, this was 17 (95% CI, 16-18) patient-months. LIMITATIONS Data were limited to stated preferences rather than actual choice of dialysis modality. CONCLUSIONS Our study suggests that it is rare for caregivers to prefer conservative nondialytic care for family members with CKD. Home-based dialysis modalities that enable patients and their family members to travel with minimal restriction would be strongly aligned with the preferences of both parties.

Patient Views About Treatment of Stage 5 CKD: A Qualitative Analysis of Semistructured Interviews

BACKGROUND How patients choose between alternative treatments for kidney failure is poorly understood. Recent studies of chronic kidney disease report that clinical outcomes, such as life expectancy, are rarely reflected in a patients decision for type of treatment compared with nonclinical outcomes, such as time on dialysis therapy, convenience, or impact on the family. METHODS A qualitative analysis using thematic synthesis of patient views about renal replacement therapy (RRT) was undertaken. As part of a national study of patients and renal health care providers, we interviewed 95 Australian dialysis and transplant patients to explore how they perceive these alternative treatments. RESULTS 52 patients were on satellite hemodialysis therapy, 8 patients were on incenter hemodialysis therapy, 8 patients were on continuous ambulatory peritoneal dialysis therapy, 5 patients were on automated peritoneal dialysis therapy, 4 patients were on home hemodialysis therapy, and 18 patients had a functioning transplant at the time of interview. Freedom, convenience, self-care, effectiveness, and simplicity were commonly cited positive characteristics, whereas confinement, risk, family burden, pain, and time commitment were negative characteristics associated with RRTs. Characteristics were not specific to dialysis modalities, and some (eg, self-care) were seen as both positive and negative. A limitation of the study was that only 17 of 77 (22%) dialysis patients interviewed were on a home-based therapy. CONCLUSIONS Patients preferred RRTs that enhanced their freedom and autonomy and were convenient, effective, and simple. Treatments that minimized confinement and risk also were viewed positively. Our analysis suggests that patients might choose between therapies based on their perception regarding which therapy most embodies particular characteristics that minimize impact on their lifestyle. Presentation of information regarding RRTs should focus on these characteristics and the potential impact of alternative treatments on the patients and how they wish to lead their lives.

Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection.

Tenofovir disoproxil fumarate (TDF) is increasingly used in patients with chronic hepatitis B (CHB) infection. Although associated with renal toxicity in HIV-infected patients, renal dysfunction has been reported rarely in the monoinfected CHB population. To date, TDF-associated Fanconi syndrome has not been reported. Here, we present two cases of TDF-associated Fanconi syndrome with rapid resolution after its cessation. We then discuss risk factors for TDF nephrotoxicity and its implications for screening for renal disease in those patients with CHB monoinfection on TDF, and the use of TDF in at-risk populations.

Barriers to Timely Arteriovenous Fistula Creation: A Study of Providers and Patients

BACKGROUND Current clinical practice guidelines recommend a native arteriovenous fistula (AVF) as the vascular access of first choice. Despite this, most patients in western countries start hemodialysis therapy using a catheter. Little is known regarding specific physician and system characteristics that may be responsible for delays in permanent access creation. STUDY DESIGN Multicenter cohort study using mixed methods; qualitative and quantitative analysis. SETTING & PARTICIPANTS 9 nephrology centers in Australia and New Zealand, including 319 adult incident hemodialysis patients. PREDICTOR Identification of barriers and enablers to AVF placement. OUTCOMES Type of vascular access used at the start of hemodialysis therapy. MEASUREMENTS Prospective data collection included data concerning predialysis education, interviews of center staff, referral times, and estimated glomerular filtration rate (eGFR) at AVF creation and dialysis therapy start. RESULTS 319 patients started hemodialysis therapy during the 6-month period, 39% with an AVF and 59% with a catheter. Perceived barriers to access creation included lack of formal policies for patient referral, long wait times for surgical review and access placement, and lack of a patient database for management purposes. eGFR thresholds at referral for and creation of vascular accesses were considerably lower than appreciated (in both cases, median eGFR of 7 mL/min/1.73 m(2)), with median wait times for access creation of only 3.7 weeks. First assessment by a nephrologist less than 12 months before dialysis therapy start was an independent predictor of catheter use (OR, 8.71; P < 0.001). Characteristics of the best performing centers included the presence of a formalized predialysis pathway with a centralized patient database and low nephrologist and surgeon to patient ratios. LIMITATIONS A limited number of patient-based barriers was assessed. Cross-sectional data only. CONCLUSIONS A formalized predialysis pathway including patient education and eGFR thresholds for access placement is associated with improved permanent vascular access placement.

Buttonhole Cannulation and Clinical Outcomes in a Home Hemodialysis Cohort and Systematic Review

BACKGROUND AND OBJECTIVES The relative merits of buttonhole (or blunt needle) versus rope ladder (or sharp needle) cannulation for hemodialysis vascular access are unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Clinical outcomes by cannulation method were reviewed in 90 consecutive home hemodialysis patients. Initially, patients were trained in rope ladder cannulation. From 2004 on, all incident patients were started on buttonhole cannulation, and prevalent patients were converted to this cannulation method. Coprimary outcomes were arteriovenous fistula-attributable systemic infections and a composite of arteriovenous fistula loss or requirement for surgical intervention. Secondary outcomes were total arteriovenous fistula-related infections and staff time requirements. Additionally, a systematic review evaluating infections by cannulation method was performed. RESULTS Seventeen systemic arteriovenous fistula-attributable infections were documented in 90 patients who were followed for 3765 arteriovenous fistula-months. Compared with rope ladder, buttonhole was not associated with a significantly higher rate of systemic arteriovenous fistula-attributable infections (incidence rate ratio, 2.71; 95% confidence interval, 0.66 to 11.09; P=0.17). However, use of buttonhole was associated with a significantly higher rate of total arteriovenous fistula infections (incidence rate ratio, 3.85; 95% confidence interval, 1.66 to 12.77; P=0.03). Initial and ongoing staff time requirements were significantly higher with buttonhole cannulation. Arteriovenous fistula loss or requirement for surgical intervention was not different between cannulation methods. A systematic review found increased arteriovenous fistula-related infections with buttonhole compared with rope ladder in four randomized trials (relative risk, 3.34; 95% confidence interval, 0.91 to 12.20), seven observational studies comparing before with after changes (relative risk, 3.15; 95% confidence interval, 1.90 to 5.21), and three observational studies comparing units with different cannulation methods (relative risk, 3.27; 95% confidence interval, 1.44 to 7.43). CONCLUSION Buttonhole cannulation was associated with higher rates of infectious events, increased staff support requirements, and no reduction in surgical arteriovenous fistula interventions compared with rope ladder in home hemodialysis patients. A systematic review of the published literature found that buttonhole is associated with higher risk of arteriovenous fistula-related infections.