Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.

Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.

Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p < 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.

Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.

Improving the identification and treatment of depression in women after acute myocardial infarction

We read with interest the article by Smolderen et al (1), which reported real-world lessons from the implementation of an American Heart Association (AHA) recommended depression screening protocol in Acute Myocardial Infarction (AMI) patients. After implementing a routine, two- step depression screening process using the Patient Health Questionnaire (PHQ) 2 and 9, the study revealed that more than 1 in 4 (n=135, 26.8%) Coronary Artery Disease (CAD) patients failed to be screened for depression. Specifically, women were likely to be missed. Of those who were screened, almost 7 of 10 patients with significant depressive symptoms failed to be recognized and thus were ineligible for treatment.

Treatment of ametryn in wastewater by a hybrid MBR system : a lab-scale study

Agricultural discharge of herbicides to the Great Barrier Reef (GBR) poses significant threat to the marine ecosystem. This study evaluates the performance of a hybrid treatment system consists of a membrane bioreactor (MBR), UV disinfection unit and a granular activated carbon (GAC) column in treating ametryn which is one of the major herbicides in agricultural discharges. While the MBR alone removes only 40% of ametryn at a hydraulic retention time of 7.8 h, the hybrid system removed ametryn to below detection levels.

Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.

Evaluation of the giant reed (Arundo donax) in horizontal subsurface flow wetlands for the treatment of dairy processing factory wastewater

Two emergent macrophytes, Arundo donax and Phragmites australis, were established in experimental horizontal subsurface flow (HSSF), gravel-based constructed wetlands (CWs) and challenged by treated dairy processing factory wastewater with a median electrical conductivity of 8.9 mS cm−1. The hydraulic loading rate was tested at 3.75 cm day−1. In general, the plants grew well during the 7-month study period, with no obvious signs of salt stress. The major water quality parameters monitored (biological oxygen demand (BOD), suspended solids (SS) and total nitrogen (TN) but not total phosphorus) were generally improved after the effluent had passed through the CWs. There was no significance different in removal efficiencies between the planted beds and unplanted gravel beds (p > 0.007), nor was there any significant difference in removal efficiencies between the A. donax and P. australis beds for most parameters. BOD, SS and TN removal in the A. donax and P. australis CWs was 69, 95 and 26 % and 62, 97 and 26 %, respectively. Bacterial removal was observed but only to levels that would allow reuse of the effluent for use on non-food crops under Victorian state regulations. As expected, the A. donax CWs produced considerably more biomass (37 ± 7.2 kg wet weight) than the P. australis CWs (11 ± 1.4 kg wet weight). This standing crop equates to approximately 179 and 68 tonnes ha−1 year−1 biomass (dry weight) for A. donax and P. australis, respectively (assuming a 250-day growing season and single-cut harvest). The performance similarity of the A. donax and P. australis planted CWs indicates that either may be used in HSSF wetlands treating dairy factory wastewater, although the planting of A. donax provides additional opportunities for secondary income streams through utilisation of the biomass produced.

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.

Early diagnosis and treatment of necrotizing fasciitis can improve survival : an observational intensive care unit cohort study

Background
The aim of this study was to describe the clinical characteristics, causative pathogens, clinical management and outcomes of patients presenting to a tertiary adult Australian intensive care unit (ICU) with a diagnosis of necrotizing fasciitis (NF).
Methods
This retrospective observational study was conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional hospital. Clinical databases were accessed for patients diagnosed with NF and admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011. Information on severity of sepsis, surgical procedures and microbiological results were collected.
Results
Twenty patients with NF were identified. The median age was 52.5 years and 38% were female. The overall mortality rate was 8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although 50% of patients had no co-morbidities. Group A Streptococcus was the identified pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%) patients. Hyperbaric oxygen therapy was not used in the majority of patients. The initial antibiotics administered were active against subsequently cultured bacteria in 83% of patients. Median time to surgical debridement was 20 h. Diagnosis and management was delayed in the nosocomial group.
Conclusions
This study reports physiological data, aetiology and therapeutic interventions in NF for an adult tertiary hospital. We demonstrate one of the lowest reported mortality rates, with early surgical debridement being achieved in the majority of patients. The main delay was found to be in the diagnosis of NF.

Self-monitoring in the treatment of overweight adolescents

The aim of this study was to explore the relationship between the quantity and quality of self-monitoring and per cent fat loss in overweight and obese adolescents participating in a weight-loss intervention. Participants were 55 (33F) overweight and obese adolescents taking part in a 20-week cognitive–behavioural intervention aimed at improving eating and physical activity behaviours. Food and physical activity self-monitoring from the first 9 weeks of the intervention was coded using 24 components assessing the quantity (20) and quality (4) of selfmonitoring. Those who completed treatment (n = 42) were split into groups: Losers (n = 30) and Gainers (n = 12) of per cent body fat as measured by DXA. Group analyses showed that Losers and Gainers could be differentiated by both quantitative and qualitative measures of self-monitoring. The strongest associations were with the classifications of food and drink items into food groups. The number of days monitored and the average number of items recorded did not differentiate the groups. Quantity and quality measures of self-monitoring completed early in treatment could also differentiate those who completed treatment and those who did not complete treatment (n = 13), and the strongest associations were with the amounts of food and drink items recorded, an association not found with treatment outcome. The results indicate that both quantity and quality of self-monitoring may be important predictors of both treatment completion and outcome. Based on these findings a framework of self-monitoring requirements is offered to reduce homework burden while maximising treatment efficacy.