Mycobacterium ulcerans infection : factors influencing diagnostic delay

Objective: To document the epidemiology, clinical characteristics and diagnosis of an outbreak of Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer [BU]) during the period 1998–2006, and compare delays in diagnosis between residents of endemic and non-endemic regions.

Design and setting: Retrospective case study of patients identified through infectious disease physicians on the Bellarine Peninsula and the Victorian Department of Human Services notifiable diseases database.

Main outcome measures: Description of events leading to diagnosis of BU.

Results: Eighty-five BU patients recalled their experience. Fifty-three patients were older than 60 years, and 61 permanently resided on the Bellarine Peninsula. The onset of symptoms occurred most frequently in mid winter. Twenty-eight patients had lesions on the arm and 51 on the leg. The median time between onset of symptoms and first medical contact was shorter for those living in the endemic area (3.0 weeks; interquartile range [IQR], 1.0–5.0 weeks) compared with non-endemic areas (5.3 weeks; IQR, 2.0–9.5 weeks) (P = 0.05). Patients who resided in the endemic area had a shorter median time from their first medical appointment to diagnosis (1.0 week; IQR, 0.0–3.9 weeks) than those who resided in non-endemic areas (5.0 weeks; IQR, 1.3–8.0 weeks) (P = 0.001).

Conclusion: Delay in presentation and time to diagnosis of BU are longer in non-endemic than endemic areas. Measures should be taken to raise awareness of the disease in non-endemic areas.

Debating the evidence : oral contraceptives containing drospirenone and risk of blood clots

Skepticism is an essential quality in science. We doubt, re-examine and demand the highest quality of evidence. However, sometimes this puts us in an awkward situation. How much evidence do we need before we act? This dilemma is a constant problem in drug safety. Treatment decisions are always a balance of risks and benefits and there may be a paucity of evidence about rare or very rare adverse events.

Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans : an observational cohort study

Background: The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of
fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia.

Methodology/Principal Findings: Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was
62 years (range 3–94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic
regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p,0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27–2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases.

Conclusions: Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.

The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers

Objective: To investigate if a lower dose of arginine in the form of an oral nutritional supplement can show similar benefit in the healing rate of pressure ulcers compared with the current evidence for 9g of arginine.

Method: Twenty-three inpatients with category II, III or IV pressure ulcers were randomised to receive daily, for 3 weeks, the standard hospital diet plus 4.5 or 9g arginine in the form of a commercial supplement. Pressure ulcer size and severity was measured weekly (by PUSH tool; pressure ulcer scale for healing; 0= completely healed, 17= greatest severity). Nutritional status was determined by Subjective Global Assessment.

Results: There were no significant differences in patients’ age, gender, BMI, haemoglobin levels, albumin levels and diagnosis of diabetes between treatment groups. There was a significant decrease in pressure ulcer severity over time (p < 0.001), with no evidence of a difference in healing rate between the two arginine dosages (p=0.991). Based on expected healing time, patients in both treatment groups were estimated to achieve an almost 2-fold improvement compared with the historical control group. Patients categorised as malnourished showed clinically significant impaired healing rates compared with wellnourished patients (p=0.057), although this was unaffected by arginine dosage (p=0.727).

Conclusion: Similar clinical benefits in healing of pressure ulcers can be achieved with a lower dosage of arginine, which can translate into improved concordance and significant cost-savings for both the health-care facilities and for patients.

A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality

Both a larger waist and narrow hips are associated with heightened risk of diabetes, cardiovascular diseases and premature mortality. We review the risk of these outcomes for levels of waist and hip circumferences when terms for both anthropometric measures were included in regression models. MEDLINE and EMBASE were searched (last updated July 2012) for studies reporting the association with the outcomes mentioned earlier for both waist and hip circumferences (unadjusted and with both terms included in the model). Ten studies reported the association between hip circumference and death and/or disease outcomes both unadjusted and adjusted for waist circumference. Five studies reported the risk associated with waist circumference both unadjusted and adjusted for hip circumference. With the exception of one study of venous thromboembolism, the full strength of the association between either waist circumference or hip circumference with morbidity and/or mortality was only apparent when terms for both anthropometric measures were included in regression models. Without accounting for the protective effect of hip circumference, the effect of obesity on risk of death and disease may be seriously underestimated. Considered together (but not as a ratio measure), waist and hip circumference may improve risk prediction models for cardiovascular disease and other outcomes.

Impact on hemostatic parameters of interrupting sitting with intermittent activity

Introduction: Excessive sitting has been associated with an elevated risk of vascular conditions, particularly venous thrombosis. Interrupting sitting time with intermittent physical activity can reduce venous stasis; however, impacts on other aspects of thrombogenesis are less understood. Purpose: To examine the effects of interrupting sitting time on blood coagulation and blood volume parameters in sedentary, middle-age, overweight/obese adults (11 men and 8 women; age = 53.8 T 4.9 yr, body mass index = 31.2 T 4.1 kgImj2; mean T SD). Methods: The randomized three-period, three-treatment acute crossover trial consisted of uninterrupted sitting and sitting interrupted by 2-min bouts of either light- or moderate-intensity treadmill walking every 20 min. In each trial condition, blood samples were collected at baseline before the consumption of a standardized meal (j2 h) and postintervention (5 h). Results: Plasma fibrinogen increased from baseline with uninterrupted sitting (0.24 gILj1, 95% confidence interval = 0.13–0.34, P G 0.001). Lightintensity but not moderate-intensity activity breaks attenuated the increase by 0.17 gILj1 (95% confidence interval = 0.01–0.32, P G 0.05). There were no between-condition differences in prothrombin time, activated partial thromboplastin time, von Willebrand
factor, D-dimer, or platelet count. Uninterrupted sitting reduced plasma volume and increased hematocrit, hemoglobin, and red blood cell count; effects attenuated by both light- and moderate-intensity breaks (P G 0.05). White blood cell count increased with uninterrupted sitting and further increased with moderate-intensity breaks. Mean platelet volume increased with moderate-intensity but not lightintensity breaks or uninterrupted sitting. Conclusion: Uninterrupted sitting increased fibrinogen and reduced plasma volume, with associated increases in hemoglobin and hematocrit. Activity breaks attenuated these responses, indicative of an ameliorating influence on the procoagulant effects of uninterrupted sitting.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.

A comparison of maternal calcium and magnesium levels in pre-eclamptic and normotensive pregnancies: an observational case–control study

Objective : Supplementing pregnant women at high risk of developing pre-eclampsia with calcium may reduce the incidence of the disease. This study examines differences in serum and hair concentrations of calcium and magnesium between women with pre-eclamptic and normotensive pregnancies.Design : Observational case–control study.Setting : Two teaching hospitals in Cape Town, South Africa.PopulationWomen with pre-eclamptic (N = 96) or normotensive (N = 96) pregnancies, who delivered a single, live infant.MethodsDemographic and current pregnancy details were retrieved from clinical notes. Each participant completed a dietary questionnaire. Venous blood samples were taken from each participant to assess serum calcium and magnesium concentrations. Hair samples were obtained from all participants and calcium and magnesium levels were measured by inductively coupled plasma optical emission spectrometry (ICPOES).Main outcome measureHair and serum calcium and magnesium concentrations were compared between women with pre-eclamptic and normotensive pregnancies.ResultsDiet and socio-economic status in the two groups were similar. There was no significant difference in the hair calcium level between women with pre-eclamptic [1241 parts per million (ppm); range, 331–4654 ppm] and normotensive (1146 ppm; range, 480–4136 ppm) pregnancies (P = 0.5). Hair calcium levels in both groups were not affected by HIV infection.ConclusionWoman with pre-eclampsia showed no difference in chronic calcium status relative to normotensive women. This finding does not support the current belief that the mechanism by which calcium supplementation reduces the risk of developing pre-eclampsia is by correcting a nutritional deficiency.

Renal access coordinators' impact on hemodialysis patient outcomes and associated service delivery: a systematic review

Background
Renal access coordinators contribute specifically to dialysis access care for people with chronic and end stage renal disease. Since the introduction of renal access coordinators into Australia in the early 2000s, there have been anecdotal examples of associated improvements in patient outcomes and service delivery; however scant published quantitative evidence exists. Thus, the impact of the implementation of renal access coordinators has not undergone a rigorous review to date.

Objective
The objective of this systematic review was to critically appraise and synthesize the best available evidence related to the impact of renal access coordinators on dialysis patient outcomes and associated service delivery.

INCLUSION CRITERIA

Types of participants
This review considered studies that included renal access coordinators (noting variations of the titles) and adult hemodialysis patients (aged 18 years and over).

Types of intervention(s)
This review considered studies that evaluated the effectiveness of the renal access coordinator. This role typically consists of clinical and administration duties such as providing pre dialysis access coordination, access surveillance patient education and nurse education.

Types of studies
The types of studies considered within this review included experimental and epidemiological study designs. Thus randomized controlled trials (RCT), non-randomized controlled trials, and quasi-experimental, before and after studies, prospective and retrospective cohort studies were considered as were case control studies, analytical cross sectional studies and descriptive cross sectional studies.

Types of outcomes
Patient outcomes considered included: days to first vascular access complication (such as stenosis or thrombosis) and/or primary intervention (such as angioplasty or surgical intervention); percentage of central line insertions (negative); rate of arteriovenous fistula (AVF)/arteriovenous graft (AVG)/central venous catheter (CVC) at start of dialysis (incidence); prevalent rate of AVF/AVG/CVC; time to occlusion of AVF and time from referral to surgery. Service outcomes included: knowledge/up skilling of renal nurses; cannulation skills, ultrasound skills, knowledge of anatomy and physiology and other access related knowledge.

Search strategy
The search strategy aimed to locate published and unpublished studies, utilizing a three-step searching approach. Studies published in English from 1990 to October 2013 were considered for inclusion in this review.

Methodological quality
The studies were assessed by two independent reviewers using the appropriate standardized critical appraisal instruments from the Joanna Briggs Institute.

Data collection
Data were extracted from papers included in the review using the standardised data extraction tool from the Joanna Briggs Institute, namely JBI Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI).

Data synthesis
This review aimed to conduct meta-analyses of the findings: however, because of the limitations of the data found, this was not possible and so the findings are presented in a narrative format.

Results
Five studies were identified for inclusion in the review. No RCTs were found, therefore four of the five studies were pre-post intervention cohort studies and one was a prospective quality assurance report. Data were heterogeneous and thus did not allow for meta-analysis. All studies included multidisciplinary teams with variable emphasis on the renal access coordinator role. The pre post intervention cohort studies measured incident and/or prevalent AVF, AVG and CVC rates in the hemodialysis population and the quality assurance report measured the difference in patency rates between AVF and AVG. All discussed the role of central coordination as a contributor to the success of vascular access care.

Conclusions
This review found insufficient data to make firm conclusions about the impact that renal access coordinators have on patient outcomes. The results of this review suggest an association between renal access coordinators and improved patient outcomes. These improved patient outcomes were apparent in an increase in incident and prevalent AVFs, and a decrease in the incidence and prevalence of CVCs. Both associations are correlated with a reduction in infection rates, length of hospital stay and healthcare costs.

Interleukin-6 and tumor necrosis factor-α are not increased in patients with type 2 diabetes: Evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness

Aims/hypothesis. Our aim was to examine the possible direct relationship of interleukin-6 and TNFα with insulin sensitivity in humans. Methods. We carried out two series of euglycaemic-hyperinsulinaemic clamp experiments. In the first (CLAMP1), skeletal muscle mRNA expression and plasma concentrations of IL-6 and TNFα were examined in patients with Type 2 diabetes (n=6), subjects matched for age (n=6), and young healthy (n=11) control subjects during a 120-min supra-physiological hyperinsulinaemic (40 mU·m -2·min-1) euglycaemic clamp. In the second series of experiments (CLAMP2), patients with Type 2 diabetes (n=6) and subjects matched for age (n=7) were studied during a 240-min high-physiological hyperinsulinaemic (7 mU·m-2·min-1) euglycaemic clamp, during which arterial and venous (femoral and subclavian) blood samples were measured for IL-6 and TNFα flux. Results. In both experiments the glucose infusion rate in the patients was markedly lower than that in the other groups. In CLAMP1, basal skeletal muscle IL-6 and TNFα mRNA were the same in all groups. They were not affected by insulin and they were not related to the glucose infusion rate. In CLAMP2, neither cytokine was released from the arm or leg during insulin stimulation in either group. In both experiments plasma concentrations of these cytokines were similar in the patients and in the control subjects, although in CLAMP1 the young healthy control group had lower (p<0.05) plasma IL-6 concentrations. Using data from all subjects, a strong positive correlation (r=0.85; p<0.00001) was observed between basal plasma IL-6 and BMI. Conversely, a negative relationship (r=-0.345; p<0.05) was found between basal plasma TNFα and BMI, although this was not significant when corrected for BMI. When corrected for BMI, no relationship was observed between either basal plasma IL-6 or TNFα and GIR. Conclusions/interpretation. These data show that the increased circulating IL-6 concentrations seen in patients with Type 2 diabetes are strongly related to fat mass and not insulin responsiveness, and suggest that neither IL-6 nor TNFα are indicative of insulin resistance.

Assessing pressure injury risk and prevention using the Braden mobility subscale

 Getting a pressure injury or ulcer whilst in hospital may cause debilitating physical effects, pain or even death. This research found that assessment of mobility alone compares well with the more commonly used and more complex risk assessment scales when used to identify person's risk for developing a pressure sore.

The cost-benefit of using soft silicone multilayered foam dressings to prevent sacral and heel pressure ulcers in trauma and critically ill patients: a within-trial analysis of the Border Trial.

Little is known about the cost-benefit of soft silicone foam dressings in pressure ulcer (PU) prevention among critically ill patients in the emergency department (ED) and intensive care unit (ICU). A randomised controlled trial to assess the efficacy of soft silicone foam dressings in preventing sacral and heel PUs was undertaken among 440 critically ill patients in an acute care hospital. Participants were randomly allocated either to an intervention group with prophylactic dressings applied to the sacrum and heels in the ED and changed every 3 days in the ICU or to a control group with standard PU prevention care provided during their ED and ICU stay. The results showed a significant reduction of PU incidence rates in the intervention group (P = 0·001). The intervention cost was estimated to be AU$36·61 per person based on an intention-to-treat analysis, but this was offset by lower downstream costs associated with PU treatment (AU$1103·52). Therefore, the average net cost of the intervention was lower than that of the control (AU$70·82 versus AU$144·56). We conclude that the use of soft silicone multilayered foam dressings to prevent sacral and heel PUs among critically ill patients results in cost savings in the acute care hospital.

A randomised controlled trial of the effectiveness of soft silicone multi-layered foam dressings in the prevention of sacral and heel pressure ulcers in trauma and critically ill patients: The border trial

The prevention of hospital acquired pressure ulcers in critically ill patients remains a significant clinical challenge. The aim of this trial was to investigate the effectiveness of multi-layered soft silicone foam dressings in preventing intensive care unit (ICU) pressure ulcers when applied in the emergency department to 440 trauma and critically ill patients. Intervention group patients (n = 219) had Mepilex^® Border Sacrum and Mepilex^® Heel dressings applied in the emergency department and maintained throughout their ICU stay. Results revealed that there were significantly fewer patients with pressure ulcers in the intervention group compared to the control group (5 versus 20, P = 0·001). This represented a 10% difference in incidence between the groups (3·1% versus 13·1%) and a number needed to treat of ten patients to prevent one pressure ulcer. Overall there were fewer sacral (2 versus 8, P = 0·05) and heel pressure ulcers (5 versus 19, P = 0·002) and pressure injuries overall (7 versus 27, P = 0·002) in interventions than in controls. The time to injury survival analysis indicated that intervention group patients had a hazard ratio of 0·19 (P = 0·002) compared to control group patients. We conclude that multi-layered soft silicone foam dressings are effective in preventing pressure ulcers in critically ill patients when applied in the emergency department prior to ICU transfer.