Evidence-based recommendations for the monitoring and treatment of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64-100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.

Current treatment of Helicobacter pylori infection and peptic ulcer disease

Since the initial report by Warren and Marshall in 1984, Helicobacter pylori has assumed an increasingly important role in the pathogenesis of peptic ulcer disease and gastric carcinoma in all ages. A recent National Institutes of Health Consensus Development conference acknowledges the relationship between H. pylori infection and peptic ulcer disease and recommends that the medical community treat H. pylori infection in all patients with Helicobacter pylori and peptic ulcer. Although the same organism, the response to Helicobacter pylori infection in childhood differs somewhat from that seen in adults. The paediatric patient mounts a different inflammatory response, has different macroscopic appearances and has a markedly diminished peptic ulcer disease frequency compared with their adult counterparts. The appearances of antral nodularity appear to be characteristic of Helicobacter pylori infections. The appearances, however, are unrelated to symptoms and the underlying cause for this nodularity remains obscure. Younger children with peptic ulcer diseases are more likely to be Helicobacter pylori negative. This may suggest an increased susceptibility to gastric acid or possibly a very transient Helicobacter pylori infection rather than the well described lifelong infection without treatment. It is well known that the epidemiology of Helicobacter pylori would suggest that the incidence of infection increases with age. There is also geographical variations with the incidence being higher in countries of a third world background. These epidemiological observations fly in the face of all other infections where the major period of acquisition is in childhood. There has been recent evidence to suggest that in fact the incidence in childhood is decreasing in developed countries which could support the observation that there is a decreasing positive serology with successive decades in some countries. It is felt that the most likely mode of transmission of Helicobacter pylori is faecal to oral or oral to oral route. These are similar modes of transmission to Hepatitis A infections. It is obvious that most infections in childhood remain asymptomatic. It is also clear that there is no relationship between chronic recurrent abdominal pain of childhood syndrome and the presence of Helicobacter pylori infections. It remains to be seen as to who should be treated, what with and when. All of these issues will be discussed in the paper.

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

The treatment of recurrent abdominal pain in children : a controlled comparison of cognitive-behavioral family intervention and standard pediatric care

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

Evaluation of ion exchange as a pre-treatment option for coal seam gas water

The Coal Seam Gas (CSG) industry in Australia has grown significantly in recent years. During the gas extraction process, water is also recovered which is brackish in character. In order to facilitate beneficial reuse of the water, the CSG industry has primarily invested in Reverse Osmosis (RO) as the primary method for associated water desalination. However, the presence of alkaline earth ions in the water combined with the inherent alkalinity of the water may result in RO membrane scaling. Consequently, weak acid cation (WAC) synthetic ion exchange resins were investigated as a potential solution to this potential problem. It was shown that resins were indeed highly efficient at treating single and multi-component solutions of alkaline earth ions. The interaction of the ions with the resin was found to be considerably more complex that previously reported.

The short-term impact of curative colorectal cancer treatment on physical activity, functional status and quality of life: A systematic review protocol

REVIEW QUESTION/OBJECTIVE The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis. INCLUSION CRITERIA Types of participants: This review will consider studies that include individuals aged 18 years and over who have been diagnosed with colorectal cancer. Types of intervention(s)/phenomena of interest: This review will consider studies that evaluate the impact of curative colorectal cancer treatment: surgery and/or adjuvant therapy. Types of outcomes: This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment: Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure. Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers, or subjectively using self-reported measures. Functional status – measured as the capacity to perform all activities of daily living such as walking, showering, and eating; and instrumental activities of daily living such as (but not limited to) grocery shopping, housekeeping and laundry. Quality of life – defined as the individual meaning of mental, physical and psychosocial wellbeing, as measured by validated tools such as SF-36, EORTC-QLQ-C30, or FACT-C.

Rank regression for analyzing ordinal qualitative data for treatment comparison

Ordinal qualitative data are often collected for phenotypical measurements in plant pathology and other biological sciences. Statistical methods, such as t tests or analysis of variance, are usually used to analyze ordinal data when comparing two groups or multiple groups. However, the underlying assumptions such as normality and homogeneous variances are often violated for qualitative data. To this end, we investigated an alternative methodology, rank regression, for analyzing the ordinal data. The rank-based methods are essentially based on pairwise comparisons and, therefore, can deal with qualitative data naturally. They require neither normality assumption nor data transformation. Apart from robustness against outliers and high efficiency, the rank regression can also incorporate covariate effects in the same way as the ordinary regression. By reanalyzing a data set from a wheat Fusarium crown rot study, we illustrated the use of the rank regression methodology and demonstrated that the rank regression models appear to be more appropriate and sensible for analyzing nonnormal data and data with outliers.

General ranked set sampling for efficient treatment comparisons

In treatment comparison experiments, the treatment responses are often correlated with some concomitant variables which can be measured before or at the beginning of the experiments. In this article, we propose schemes for the assignment of experimental units that may greatly improve the efficiency of the comparison in such situations. The proposed schemes are based on general ranked set sampling. The relative efficiency and cost-effectiveness of the proposed schemes are studied and compared. It is found that some proposed schemes are always more efficient than the traditional simple random assignment scheme when the total cost is the same. Numerical studies show promising results using the proposed schemes.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.

Use of electronic portal imaging devices for electron treatment verification

This study aims to help broaden the use of electronic portal imaging devices (EPIDs) for pre-treatment patient positioning verification, from photon-beam radiotherapy to photon- and electron-beam radiotherapy, by proposing and testing a method for acquiring clinicallyuseful EPID images of patient anatomy using electron beams, with a view to enabling and encouraging further research in this area. EPID images used in this study were acquired using all available beams from a linac configured to deliver electron beams with nominal energies of 6, 9, 12, 16 and 20 MeV, as well as photon beams with nominal energies of 6 and 10 MV. A widely-available heterogeneous, approximately-humanoid, thorax phantom was used, to provide an indication of the contrast and noise produced when imaging different types of tissue with comparatively realistic thicknesses. The acquired images were automatically calibrated, corrected for the effects of variations in the sensitivity of individual photodiodes, using a flood field image. For electron beam imaging, flood field EPID calibration images were acquired with and without the placement of blocks of water-equivalent plastic (with thicknesses approximately equal to the practical range of electrons in the plastic) placed upstream of the EPID, to filter out the primary electron beam, leaving only the bremsstrahlung photon signal. While the electron beam images acquired using a standard (unfiltered) flood field calibration were observed to be noisy and difficult to interpret, the electron beam images acquired using the filtered flood field calibration showed tissues and bony anatomy with levels of contrast and noise that were similar to the contrast and noise levels seen in the clinically acceptable photon beam EPID images. The best electron beam imaging results (highest contrast, signal-to-noise and contrast-to-noise ratios) were achieved when the images were acquired using the higher energy electron beams (16 and 20 MeV) when the EPID was calibrated using an intermediate (12 MeV) electron beam energy. These results demonstrate the feasibility of acquiring clinically-useful EPID images of patient anatomy using electron beams and suggest important avenues for future investigation, thus enabling and encouraging further research in this area. There is manifest potential for the EPID imaging method proposed in this work to lead to the clinical use of electron beam imaging for geometric verification of electron treatments in the future.

Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac diseases. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immunoreactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

Treatment of distal intestinal obstruction syndrome in cystic fibrosis with a balanced intestinal lavage solution

Conventional treatment of distal intestinal obstruction syndrome (DIOS) with high doses of pancreatic enzymes, mucolytic agents, and enemas is neither predictably effective nor rapid in action. In 6 cystic fibrosis patients with DIOS a balanced, non-absorbable intestinal lavage solution produced clinical and radiological improvement and striking improvement in DIOS scores. It is suggested that a balanced intestinal lavage solution should be considered as an alternative treatment for DIOS in patients with cystic fibrosis.

A dosimetric retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC)

Purpose A retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC). Methods and materials Five randomly selected early stage lung cancer patients were included in the study. For each patient, four plans were created: the SBRT plan and three VMAT plans using different optimisation methodologies. A total of 20 different plans were evaluated. The dose parameters of dose conformity results and the target dose constraints results were compared for these plans. Results The mean planning target volume (PTV) for all the plans (SBRT and VMAT) was 18·3 cm3, with a range from 15·6 to 20·1 cm3. The maximum dose tolerance to 1 cc of all the plans was within 140% (84 Gy) of the prescribed dose, and 95% of the PTV of all the plans received 100% of the prescribed dose (60 Gy). In all the plans, 99% of the PTV received a dose >90% of the prescribed dose, and the mean dose in all the plans ranged from 67 to 72 Gy. The planning target dose conformity for the SBRT and the VMAT (0°, 15° collimator single arc plans and dual arc) plans showed the tightness of the prescription isodose conformity to the target. Conclusions SBRT and VMAT are radiotherapy approaches that increase doses to small tumour targets without increasing doses to the organs at risk. Although VMAT offers an alternative to SBRT for NSCLC and the potential advantage of VMAT is the reduced treatment times over SBRT, the statistical results show that there was no significant difference between the SBRT and VMAT optimised plans in terms of dose conformity and organ-at-risk sparing.

Pavement management: Capturing surface treatment effectiveness

Acquiring detailed knowledge of surface treatments effectiveness is required to improve performance-based decisions for allocating resources to preserve and maintain pavements on any road network. Measurement of treatment effectiveness is a complex task that requires historical records of treatments with observations of before and after performance trends. Lack of data is often an obstacle that impedes development and incorporation of surface maintenance treatments into pavement management. This paper analyzes the effect of surface treatments on asphalt paved arterial roads for several control sections of New Brunswick. The method uses a Transition Probability Matrix to capture main effects by mapping mean trends of surface improvement and pavement structure decay. It was found that surface treatments have an immediate effect reducing the rate of loss of structural capacity. Pavements with international roughness index (IRI) smaller than 1.4 m/km did not seem to benefit from surface treatments. Those with IRI higher than 1.66 m/km gained from 6 to 8 years of additional life. Reset value for surface treatments fall between 1.18 and 1.29 m/km. This paper aims to serve to practitioners seeking to capture and incorporate effectiveness of surface treatments (i.e., crack-sealing) into Pavement Management.