Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort

Objective: To describe risk factors for recurrence after exclusive surgical treatment of Mycobacterium ulcerans infection. Design, setting and participants: Prospective observational cohort study of all M. ulcerans cases managed with surgery alone at Barwon Health, a tertiary referral hospital, from 1 January 1998 to 31 December 2011. A random-effects Poisson regression model was used to assess rates and associations of treatment failure. Main outcome measures: Rates of treatment failure and rate ratios (RRs) for factors associated with treatment failure. Results: Of 192 patients with M. ulcerans infection, 50 (26%) had exclusive surgical treatment. Median age was 65.0 years (interquartile range [IQR], 45.5-77.7 years), and median duration of symptoms was 46 days (IQR, 26-90 days). There were 20 recurrences in 16 patients. For first lesions, the recurrence incidence rate was 41.8 (95% CI, 25.6-68.2) per 100 person-years, and median time to recurrence was 50 days (IQR, 30-171 days). Recurrence occurred ≤ 3 cm from the original lesion in 13 cases, and >3 cm in nine. On univariable analysis, age ≥60 years (RR 13.84; 95% CI, 2.21-86.68; P< 0.01), distal lesions (RR, 20.43; 95% CI, 1.97-212.22; P<0.01), positive histological margins (RR, 21.02; 95% CI, 5.51-80.26; P< 0.001), immunosuppression (RR, 17.97; 95% CI, 4.17-77.47; P <0.01) and duration of symptoms >75 days (RR, 10.13; 95% CI, 1.76-58.23; P =0.02) were associated with treatment failure. On multivariable analysis, positive margins (RR, 7.72; 95% CI, 2.71-22.01; P<0.001) and immunosuppression (RR, 6.45; 95% CI, 2.42-17.20; P =0.01) remained associated with treatment failure. Conclusions: Recurrence rates after exclusive surgical treatment of M. ulcerans disease in an Australian cohort are high, with increased rates associated with immunosuppression or positive histological margins.

Mycobacterium ulcerans treatment - can antibiotic duration be reduced in selected patients?

Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21–41days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14–27 days and 100% for 28–55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14–27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes.

The process of change in offender rehabilitation programmes

Whilst the overall effectiveness of offender rehabilitation programmes in reducing recidivism is now well established, there has been less discussion of the reasons why rehabilitation programmes may be unsuccessful for some offenders. In this paper we suggest that models of change developed in counselling and psychotherapy may have utility in explaining how offender rehabilitation programmes bring about change, and argue that the dominance of cognitive-behavioural treatments in the rehabilitation field means that those offenders who have particularly low levels of problem awareness may be at increased risk of treatment failure. Understanding more about the mechanisms by which programmes help offenders to desist from offending is likely to lead to the development of more responsive and, ultimately, more effective programmes. Some suggestions for those involved in the delivery of offender rehabilitation programmes include: being mindful of the sequence of components of programmes, the development of preparation (or readiness) programmes and offering a broad suite of programmes to cater for different stages of problem awareness and assimilation among offenders.

Problem assimilation and offender rehabilitation

Whilst the overall effectiveness of offender rehabilitation programs in reducing recidivism is now well established, there has been less discussion of the reasons why rehabilitation programs may be unsuccessful for some offenders. In this paper we suggest that the Assimilation model of change (Stiles et al., 1991) may have utility in explaining how offender rehabilitation programs bring about change, and argue that those offenders who have particularly low levels of problem awareness may be at increased risk of treatment failure. Methods of measuring problem awareness and treatment readiness are discussed along with possible methods of intervention, including the Pennebaker method.

Cancer stem cells in prostate cancer chemoresistance

There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets, develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated signaling pathways such as PI3K/Akt/mTOR, Wnt/β-catenin and Notch pathways in the regulation of CaP chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical outcomes of CaP patients.

Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment.

The Renal Treatment Satisfaction Questionnaire (RTSQ): a measure of satisfaction with treatment for chronic kidney failure.

BACKGROUND: Quality and effectiveness of care can be enhanced through the use of condition-specific measures of satisfaction with treatment. The aim of the present study was to design and develop a measure of satisfaction with treatment for patients with chronic kidney failure (CKF) for use in routine clinical care and clinical trials. The Renal Treatment Satisfaction Questionnaire (RTSQ) was designed to be suitable for people using any of the various treatment modalities for CKF. Items measure satisfaction with aspects of treatment, including convenience, flexibility, freedom, and satisfaction to continue with present form of treatment.

METHODS: A 12-item RTSQ was investigated at a UK hospital-based renal unit, using data from 140 outpatients undergoing renal replacement therapy (hemodialysis, n = 35; continuous ambulatory peritoneal dialysis, n = 57; transplantation, n = 46).

RESULTS: An 11-item scale was developed from the original 12-item version, with a single factor accounting for 59% of the variance and item loadings greater than 0.58. Scale reliability was excellent (alpha = 0.93) in the full sample and proved robust to analysis in separate treatment subgroups. As expected, RTSQ scores differed significantly ( P < 0.0001) between the transplantation and other treatment groups. Those who had received a transplant expressed greater overall satisfaction, with specific advantages of transplantation shown by all individual items, including convenience, time, lifestyle, freedom, and satisfaction to continue current treatment.

CONCLUSION: The RTSQ provides a brief reliable measure of satisfaction with treatment for patients with CKF that is suitable for use in routine clinical care and clinical trials.

Premature thermal fatigue failure of aluminium injection dies with duplex surface treatment

The premature failure of an aluminium injection die with a duplex surface treatment (plasma nitriding and physical vapor deposition coating) was investigated, in an effort to identify the causes of such premature failure of the component. The manufacturing and the operating conditions were documented. Analytical tools were used, including scanning electron microscopy with energy dispersive X-ray capability, X-ray diffraction, and instrumented microhardness testing. Preliminary observations showed a microstructure of coarse tempered martensite, and a considerably rough surface with porosity and cracks. A detailed analysis of crack initiation sites identified sulfur inclusions in the subsurface, underneath the coating. A further revision of the processing conditions revealed that a sulfur-impregnated grinding stone had been used to polish the die. The chemical composition of such grinding stone matched that of the inclusions found in the subsurface of the failed component. Thus, searched causes of premature failure could be discussed on the lights of the present findings.

Satisfaction with general practitioner treatment of depression among residents of aged care facilities.

Objective: This article investigates consumer perspectives on the treatment for depression among older people in residential facilities. Method: Aged care residents who were aware of being treated for depression in the past 6 months (24 women and 7 men, mean age = 83 years) participated in an interview that assessed their perspective on treatments. Results: Although more than half of the participants in the sample reported overall satisfaction with the medical treatments received for depression, qualitative data provided indications of unsatisfactory service delivery, including perceptions of low treatment efficacy, short consultation times, the failure to assess affective symptomatology, and negative responses to residents’ disclosure of symptoms. Discussion: The findings are discussed in relation to previous research on consumer satisfaction with health services and issues that may be pertinent to the elderly depressed. Training for general practitioners providing treatment in aged care is indicated.

Assessment of cognitive function in heart failure patients

Background
Research on the cognitive capacity of heart failure patients is limited, with a paucity of benchmark information available for this population. It is highly likely that cognitive deficits affect patients' understanding of disease and treatment requirements, as well as limiting their functional capacity and ability to implement treatment plans, and undertake self-care.

Aims
The purpose of this study was to establish a comprehensive neurocognitive profile of the heart failure patient through systematic neurocognitive assessment and to determine whether an association existed between severity of heart failure and cognitive abilities.

Methods
Thirty-eight patients were recruited from the heart failure patient databases of two metropolitan hospitals in Melbourne, Australia. Participants were individually assessed using four standardised, internationally recognised neuropsychological tests that examined current and premorbid intelligence, memory and executive functioning.

Results
Although there was no significant decline from premorbid general intellectual function, other specific areas of deficit, including impaired memory and executive functioning, were identified. There were no significant correlations between heart failure severity and the neurocognitive measures used.

Conclusion
The results support the need to recognise cognitive impairment in people with heart failure and to develop an abbreviated method of assessing cognitive function that can be easily implemented in the clinical setting. Identifying cognitive deficits in this population will be useful in guiding the content and nature of treatment plans to maximise adherence and minimise worsening of heart failure symptoms.

Conservative treatment of patellar tendinopathy

Patellar tendinopathy disrupts athletic careers in several sports and is resistant to many forms of conservative treatment. Outcome after conservative treatment has been minimally investigated, and the effect of these treatments on the pathology of overuse tendinopathy are not well understood.

The clinical assessment of patellar tendinopathy appears straightforward, but evidence suggests that the importance of imaging and palpation in diagnosis and ongoing assessment may be overestimated. There is a lack of clinically relevant research on which to base treatment. However, the principles of management for patellar tendinopathy derived from clinical experience include load modification, musculotendinous rehabilitation, and intervention to improve the shock absorbing capacity of the limb. The role of electrophysical agents, massage, and stretching in the treatment of patellar tendinopathy are also discussed. The progression of treatment is based on clinical grounds due to a lack of reliable subjective and objective tools to assess recovery.

The failure of some conservative programs could be due to either athlete compliance or practitioner expertise. The management of patellar tendinopathy is complex, and if the physiotherapist addresses all the principles of treatment, the chance of success could be increased.

Dying in hospital: medical failure or nature outcome?

The purpose of this study was to describe patterns of medical and nursing practice in the care of patients dying of oncological and hematological malignancies in the acute care setting in Australia. A tool validated in a similar American study was used to study the medical records of 100 consecutive patients who died of oncological or hematological malignancies before August 1999 at The Canberra Hospital in the Australian Capital Territory. The three major indicators of patterns of end-of-life care were documentation of Do Not Resuscitate (DNR) orders, evidence that the patient was considered dying, and the presence of a palliative care intention. Findings were that 88 patients were documented DNR, 63 patients' records suggested that the patient was dying, and 74 patients had evidence of a palliative care plan. Forty-six patients were documented DNR 2 days or less prior to death and, of these, 12 were documented the day of death. Similar patterns emerged for days between considered dying and death, and between palliative care goals and death. Sixty patients had active treatment in progress at the time of death. The late implementation of end-of-life management plans and the lack of consistency within these plans suggested that patients were subjected to medical interventions and investigations up to the time of death. Implications for palliative care teams include the need to educate health care staff and to plan and implement policy regarding the management of dying patients in the acute care setting. Although the health care system in Australia has cultural differences when compared to the American context, this research suggests that the treatment imperative to prolong life is similar to that found in American-based studies.

Chronic heart failure programs : does more equal less? (BENCH study)

The national multi-centre study (49 programs, 1158 patients) developed a quality score (HF-IS) and the national benchmarks for heart programs. The higher a program scored on the HF-IS the greater the reduction in hospital admissions and mortality. This score has the potential to change national nursing practice and improve health outcomes of patients.

Exercise and Sports Science Australia position statement on exercise training and chronic heart failure

Chronic heart failure (CHF) is a complex syndrome characterised by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Regular exercise participation has been shown to be a safe and effective treatment modality in the majority of CHF patients, partially reversing some of the maladaptations evident in myocardial and skeletal muscle function, and resulting in improvements in physical fitness and quality of life, and perhaps reduced mortality. The volume and intensity of exercise that is recommended depends on the syndrome severity, however in most patients it should consist of a combination of low-to-moderate intensity aerobic (endurance) exercise on most days of the week and individually prescribed low-to-moderate intensity resistance (strength) training at least twice per week. Additionally, all patients should be closely monitored prior to and during exercise for contraindications by an appropriately trained health professional. The purpose of this statement is to inform and guide exercise practitioners and health professionals in the safe and effective prescription and supervision of exercise for patients with CHF.