Revisiting the use of the EORTC QLQ-STO22 to assess health-related quality of life of patients with gastric cancer: incorporating updated treatment options and cross-cultural perspectives.

BACKGROUND: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia. METHODS: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability. RESULTS: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions. CONCLUSIONS: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.

Rapid decreases of key antioxidant molecules in critically ill patients: A personalized approach.

BACKGROUND & AIMS: Oxidative stress is regarded a key component of critical illness and has been associated with poor prognosis in Intensive Care Unit (ICU) patients. Diverse antioxidant treatments have been applied to combat oxidative stress in ICU, yet the results were typically disappointing. An explanation for this failure is that all studies utilized antioxidants indiscriminately and did not take into account the antioxidant profile of the patients. The aim of the present study was to investigate whether critically ill patients experience different insufficiencies in three major antioxidants with a "recycling" redox relationship (vitamin C, vitamin E and glutathione) and in the central reductant molecule of many enzymatic antioxidants (NADPH). METHODS: Sixty mechanically-ventilated adult medical critically ill patients (age: 63.5 ± 17.1; APACHE II score: 21.2 ± 7.4; Glasgow Coma Scale: 6.2 ± 1.9) were enrolled in the study, while 20 healthy age-matched volunteers served as control group. The antioxidant profile and the level of systemic oxidative stress (F2-isoprostanes) were measured at ICU admission and at days 1 and 7. RESULTS: The majority of the ICU patients developed rapid and severe antioxidant insufficiencies (by exhibiting less than 50% of the control values) in one (22/60), two (7/60) or three (2/60) of the antioxidants measured, despite the almost similar levels of oxidative stress. CONCLUSIONS: The wide heterogeneity in antioxidant decreases in response to ICU stay highlights the importance of patient stratification when planning to apply antioxidant treatments and indicates that the successful delivery of personalized clinical nutrition may depend on our ability to identify "responsive" phenotypes.

Renal transplantation for lupus nephritis: non-adherence and graft survival.

OBJECTIVES: Poor adherence to immunosuppressive treatment is common in patients with systemic lupus erythematosus and may identify those with lupus nephritis (LN) who have a poorer prognosis. Non-adherence has also been reported to be a potential adverse outcome predictor in renal transplantation (rTp). We investigated whether non-adherence is associated with increased rTp graft rejection and/or failure in patients with LN. METHODS: Patients with LN undergoing rTp in two major London hospitals were retrospectively included. Medical and electronic records were reviewed for documented concerns of non-adherence as well as laboratory biochemical drug levels. The role of non-adherence and other potential predictors of graft rejection/failure including demographics, comorbidities, age at systemic lupus erythematosus and LN diagnosis, type of LN, time on dialysis prior to rTp and medication use were investigated using logistic regression. RESULTS: Out of 361 patients with LN, 40 had rTp. During a median follow-up of 8.7 years, 17/40 (42.5%) of these patients had evidence of non-adherence. A total of 12 (30.0%) patients experienced graft rejection or failure or both. In the adherent group 2/23 (8.7%) had graft rejection, whilst in the non-adherent this rose to 5/17 (29.4%, p = 0.11). Graft failure was seen in 5/23 (21.7%) patients from the adherent group and 4/17 (23.5%) in the non-adherent group ( p = 0.89). Non-adherent patients had a trend towards increased graft rejection, hazard ratio 4.38, 95% confidence interval = 0.73-26.12, p = 0.11. Patients who spent more time on dialysis prior to rTp were more likely to be adherent to medication, p = 0.01. CONCLUSION: Poor adherence to immunosuppressive therapy is common and has been shown to associate with a trend towards increased graft failure in patients with LN requiring rTp. This is the first paper to report that shorter periods on dialysis prior to transplantation might lead to increased non-adherence in lupus patients.

Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7).

Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway.

Atypical case of post-partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy?

A middle-aged female patient presented with increasing dyspnoea following delivery of her second child. Echocardiography showed left ventricular (LV) dilatation and severe global impairment of systolic function (ejection fraction < 10%) but normal right ventricular (RV) dimensions. Plasma B-type natriuretic peptide level was elevated. Post-partum cardiomyopathy (PPCM) was considered and after initiating appropriate heart failure pharmacotherapy, her symptoms improved significantly. Cardiovascular MR showed RV free wall dyskinesia and aneurysms at the LV apex, RV free wall and RV outflow tract. Genetic analysis showed a C11842T substitution in the titin gene (TTN). This is the first case to propose an overlap syndrome of PPCM and arrhythmogenic RV cardiomyopathy.

How sweet is the pacemaker?

Pacemaker infections can be difficult to diagnose, especially when they present with non-specific symptoms and signs a long time after insertion of the device. Unidentified or partially treated low-grade chronic sepsis can result in multisystem disease processes with significant mortality and morbidity. Therefore, a high index of suspicion is required to identify the pacemaker as the source of sepsis and treat it effectively. This report describes a case of chronic pacemaker wire infection, which eventually presented with Sweet's syndrome, a rare manifestation of infective endocarditis.

Adjuvant therapy for resectable pancreatic adenocarcinoma: review of the current treatment approaches and future directions.

Adenocarcinoma of the pancreas carries a uniformly poor prognosis with high rates of loco-regional as well as systemic recurrence. Outcomes remain poor, even for early stage and resectable disease. It is perceived as inherently resistant to most of the currently available treatment options. Evidence supports the need for adjuvant chemotherapy but controversy remains in relation to the use of combined therapy, novel agents and the most appropriate timing of therapy. Despite no clear consensus, mainstay of treatment following resection is based primarily on single agent gemcitabine. Promising new agents and molecules of prognostic as well as predictive value under evaluation offer intriguing data, despite issues surrounding adjuvant therapy strategies. In this article, we sought to review the different therapeutic adjuvant modalities and future directions.

International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer.

BACKGROUND: Older people represent the majority of cancer patients but their specific needs are often ignored in the development of health-related quality of life (HRQOL) instruments. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-ELD15 was developed to supplement the EORTC's core questionnaire, the QLQ-C30, for measuring HRQOL in patients aged >70 years in oncology studies. METHODS: Patients (n=518) from 10 countries completed the QLQ-C30, QLQ-ELD15 and a debriefing interview. Eighty two clinically stable patients repeated the questionnaires 1 week later (test-retest analysis) and 107 others, with an expected change in clinical status, repeated the questionnaires 3 months later (response to change analysis, RCA). RESULTS: Information from the debriefing interview, factor analysis and item response theory analysis resulted in the removal of one item (QLQ-ELD15QLQ-ELD14) and revision of the proposed scale structure to five scales (mobility, worries about others, future worries, maintaining purpose and illness burden) and two single items (joint stiffness and family support). Convergent validity was good. In known-group comparisons, the QLQ-ELD14 differentiated between patients with different disease stage, treatment intention, number of comorbidities, performance status and geriatric screening scores. Test-retest and RCA analyses were equivocal. CONCLUSION: The QLQ-ELD14 is a validated HRQOL questionnaire for cancer patients aged 70 years. Changes in elderly patients' self-reported HRQOL may be related to both cancer evolution and non-clinical events.

An unusual but reversible cause of ventricular fibrillation.

A 61-year-old woman was admitted with general malaise, chest pain and breathlessness. During her inpatient stay she sustained a ventricular fibrillation (VF) arrest which was successfully terminated with direct current cardioversion. Cardiac investigations revealed poor left ventricular systolic function but unequivocally normal coronary arteries. During the course of her admission a macular rash developed and following investigations including a renal biopsy, a new diagnosis of systemic lupus erythematosus (SLE) and related myocarditis was reached. First presentation of lupus with myocarditis and VF is uncommon, however reaching the correct diagnosis is important as due to the reversible nature of the condition and improvement in left ventricular systolic function with medical therapy, an implantable cardioverter defibrillator (ICD) might not be appropriate. Our case report demonstrates the importance of screening for reversible conditions when considering ICD therapy for secondary prevention of malignant arrhythmias.

Reducing co-administration of clopidogrel and proton pump inhibitors in acute coronary syndromes.

BACKGROUND: Recent concerns about clopidogrel and proton pump inhibitor (PPI) co-administration in patients following an acute coronary syndrome (ACS) led us to investigate our practice. Guidance recommends that omeprazole and esomeprazole should not be co-administered with clopidogrel as they can decrease its efficacy. Pantoprazole and lansoprazole are safer for use in these cases. METHODS: Patients discharged between August 2008 and July 2009 with a diagnosis of ACS, on both clopidogrel and any PPI, were identified using the pharmacy database. Their notes were retrospectively reviewed, the indication for a PPI was checked and whether an appropriate one had been prescribed was assessed. As a result of our findings a simple algorithm was introduced to set out guidance on appropriate use and junior doctors were informed of the new procedure. We then performed another audit of patients discharged between August 2009 and February 2010 to ensure that the guidelines were being followed. RESULTS: During the first phase of the audit 43 out of 91 patients (47.5%) received a PPI with clopidogrel. Following our intervention, re-auditing confirmed that clopidogrel and PPI co-administration had decreased significantly to 27 out of 101 patients (26.7%) (p = 0.018). CONCLUSIONS: Through a simple intervention with an algorithm and education of junior doctors we have shown that significant improvement and adherence to guidance can be achieved.

Bone metastases: assessment of therapeutic response through radiological and nuclear medicine imaging modalities.

Radiological and nuclear medicine imaging modalities used for assessing bone metastases treatment response include plain and digitalised radiography (XR), skeletal scintigraphy (SS), dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI), [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/CT. Here we discuss the advantages and disadvantages of these assessment modalities as evident through different clinical trials. Additionally, we present the more established response criteria of the International Union Against Cancer and the World Health Organization and compare them with newer MD Anderson criteria. Even though serial XR and SS have been used to assess the therapeutic response for decades, several months are required before changes are evident. Newer techniques, such as MRI or PET, may allow an earlier evaluation of response that may be quantified through monitoring changes in signal intensity and standard uptake value, respectively. Moreover, the application of PET/CT, which can follow both morphological and metabolic changes, has yielded interesting and promising results that give a new insight into the natural history of metastatic bone disease. However, only a few studies have investigated the application of these newer techniques and further clinical trials are needed to corroborate their promising results and establish the most suitable imaging parameters and evaluation time points. Last, but not least, there is an absolute need to adopt uniform response criteria for bone metastases through an international consensus in order to better assess treatment response in terms of accuracy and objectivity.

Effectiveness of insecticides in controlling the first and second generations of the Lobesia botrana (Lepidoptera: Tortricidae) in table grapes.

The moth Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) is a key pest of table and wine grape (Vitis spp.) varieties in Cyprus. Many different insecticide combinations were applied for three consecutive years (2006-2008) in a Sultana seedless table grape vineyard, aimed at controlling the first and second generations of this pest under warm and dry Mediterranean climatic conditions. In Cyprus, Sultana is the main early maturing table grape variety grown in the country. L. botrana has two generations and a partial third on this export variety, of which the first two generations are the most destructive. Applications were made according to pheromone trap captures of males. One application was used against the first and two applications against the second generation of L. botrana. A high rate of bunch damage was observed in the untreated rows during all years, reaching 56.7, 62.5, and 69.2% in 2006, 2007, and 2008, respectively. Differences between insecticide treatments and the untreated control were statistically significant. The treatment combination of lufenuron, spinosad, and indoxacarb as well as the combination of chlorpyrifos, spinosa and indoxacarb, used against the first and second generations of L. botrana, were the most effective compared with the untreated control. Satisfactory control of the pest also was observed with other combinations such as lufenuron, cypermethrin, and Bacillus thuringiensis; chlorpyrifos, cypermethrin, and B. thuringiensis; and lufenuron, deltamethrin, and azadirachtin.

Botanical insecticides in controlling Kelly's citrus thrips (Thysanoptera: Thripidae) on organic grapefruits.

Kelly's citrus thrips, Pezothrips kellyanus (Bagnall) (Thysanoptera: Thripidae) was first recorded in Cyprus in 1996 and became an economic citrus pest. In Cyprus, Kelly's citrus thrips larvae cause feeding damage mainly on immature lemon and grapefruit fruits. Use of botanical insecticides is considered an alternative tool compared with synthetic chemicals, in offering solutions for healthy and sustainable citrus production. During 2008-2010, the efficacy of the botanical insecticides azadirachtin (Neemex 0.3%W/W and Oikos 10 EC), garlic extract (Alsa), and pyrethrins (Vioryl 5%SC) was evaluated in field trials against Kelly's citrus thrips larval stage I and II aiming at controlling the pest's population and damage to organic grapefruit fruits. In each of the trial years treatments with pyrethrins and azadirachtin (Neemex 0.3%W/W) were the most effective against Kelly's citrus thrips compared with the untreated control (for 2008: P < 0.018; for 2009: P < 0.000; for 2010: P < 0.008). In 2008, the mean number of damaged fruits in treatments with pyrethrins and Neemex was 9.6 (19.2%) and 9.7 (19.5%) respectively, compared with 12.2 (24.3%) in the untreated control. In 2009, the mean number of damaged fruits in treatment with pyrethrins was 3.7 (7.3%) and 3.9 (7.8%) in treatment with Neemex compared with 8.6 (17.3%) in the untreated control, while in 2010 the mean damaged fruits in these treatments was recorded at 18.7 (37.5%) and 19.6 (39.2), respectively, compared with 29.6 fruits (59.2%) in the control. Oikos 10 EC showed significant effect only in 2009 and 2010. In these years, the mean number of damaged fruits was recorded at 5.5 and 21.2 compared with 8.6 and 29.6 fruits in the untreated control, respectively. Garlic extract showed the lowest effect from all the botanicals used compared with the untreated control.

Ecology and behavior of Pezothrips kellyanus (Thysanoptera: Thripidae) on citrus.

The most common thrips species found in Cyprus citrus orchards between 2003 and 2008 were Pezothrips kellyanus (Bagnall) (Thysanoptera: Thripidae), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), and Thrips tabaci (Lindeman) (Thysanoptera: Thripidae). Only Pezothrips kellyanus, Kelly's citrus thrips (KCT) causes feeding damage on citrus fruits in Cyprus. KCT adults prefer to concentrate mostly in the northern and eastern sides of both lemon and grapefruit canopies. The attractiveness of white, sky blue, marine blue, and yellow color to KCT was evaluated. White was found to be the most attractive color to adults of KCT, F. occidentalis, and T. tabaci. A range of incidental and breeding host plants grown within and outside citrus orchards in Cyprus were identified. KCT adults were found on flowers of all citrus varieties, and various other flowering plants including Malva nicaeensis, Malva silvestris, Sinapis alba, Oxalis pes-caprae, Calendula arvensis, Urospermum picroides, Jasminum officinale, Gardenia jasminoides, Jasminum sambac, Prunus dulcis, Mangifera indica, Persea americana, and Eriobotrya japonica. KCT larvae were found only on lemon, grapefruit, Jasmine spp., and Gardenia flowers.

The management of metastatic bone disease with the combination of bisphosphonates and radiotherapy: from theory to clinical practice.

Bone metastases are common in the event of malignancy and are inevitably associated with serious complications that may deteriorate the quality of life (QOL) of patients and threaten life. Both radiotherapy (RT) and bisphosphonates (BPs) have an established role in the management of metastatic bone disease. Many clinical trials have demonstrated their effectiveness when used as sole treatment modalities, but only a few have evaluated their therapeutic value when applied concomitantly. We herein discuss the pathophysiology of bone metastases and the potential interactions between RT and BPs. Moreover, the results of both animal models and clinical studies are presented in detail. Apart from aspects of normal tissue tolerance, other interactions include spatial cooperation and additive or super-additive effects. The latter brings about a synergistic activity that results in an enhanced reossification, improved bone stability and microarchitecture, and increased mechanical strength, as documented through animal model studies. The results of published clinical studies investigating the effectiveness of concomitant application of RT and BPs are promising, reporting a significant clinical and radiologic response. More specifically, a significant reduction of pain scores and a worth noticing improvement in QOL and performance status (PS) were noted, accompanied by a considerable increase in bone density. Pain relief was accompanied by a marked reduction in analgesic opioid need. The enhanced reossification may be responsible for the improved therapeutic response, since it was shown that the correlation between pain and bone density is negative and strong. Although promising and encouraging, the results of such studies should be corroborated by larger, randomized trials.