The construction of a new evaluative GERD questionnaire--methods and state of the art

Gastroesophageal reflux disease (GERD) is one of the most prevalent diseases worldwide, and it is becoming increasingly important to monitor the effect of various interventions on GERD symptoms. There can be rapid temporal changes in the severity and frequency of patients' symptoms as well as their health status and well-being, all of which could, theoretically, be monitored using diaries or questionnaires. However, current GERD monitoring instruments are not appropriate because they do not assess symptoms daily, they are not sufficiently responsive to short-term changes in health status or they are not adequately validated. To address these problems, the conceptual and psychometric requirements for a GERD symptom assessment questionnaire were identified. A dimension-based scale was designed to reduce the number of symptoms monitored on a daily basis, and the validation process was defined to produce parallel long and short forms of a scale for patients' self-assessment of their GERD symptom response to therapy. These basic principles which underlie the successful development of a new, self-assessed symptomatic reflux questionnaire (ReQuest) are also applicable to the development of validated questionnaires for daily symptom self-assessment in other disease areas.     

Investigation of ethanol-induced impairment of spatial memory in γ2 heterozygous knockout mice

GABA_A receptors, the major inhibitory receptors in the mammalian central nervous system, are affected by a number of drug compounds, including ethanol. The pharmacological effects of certain drugs have been shown to be dependent upon specific GABA_A receptor subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the γ2-containing GABA_A receptors as a mechanism of action. To probe the involvement of the γ2 subunit in ethanol's actions, spatial memory for the Morris water maze task was tested in γ2 heterozygous knockout mice and wild type littermate controls following ethanol administration at the following doses: 0.0, 1.25, 1.75, and 2.25 g/kg. While baseline learning and memory were unaffected by reduction of γ2 containing GABA_A receptors, ethanol dose-dependently impaired spatial memory equally in γ2 heterozygous knockouts and wild type littermate controls.     

Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: Ameliorating effect of N-acetylcysteine and curcumin

Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.     

Venous thromboembolism in the trauma patient

Deep vein thrombosis (DVT) is a common complication amongst patients who sustain major trauma. Whilst DVT may result in long-term morbidity, it is the potential for the fatal consequences of acute pulmonary embolism (PE) that remain a significant cause for concern in the severely injured patient. The incidence and risk factors for venous thromboembolism (VTE) are discussed. The aetiology of thrombus formation in trauma is reviewed in depth.Multiple methods of thromboprophylaxis exist, both pharmacological and mechanical. Inferior venal caval filters, on the other hand, aim to prevent the emboli from DVTs that have already formed lodging within the pulmonary vasculature. All modalities have potential advantages and disadvantages.The likelihood of DVT can potentially be predicted by scoring systems, whilst numerous methods of DVT detection can be employed. Once DVT has been diagnosed, treatment should be commenced.Major trauma patients may sustain a vast array of injuries, and prevention and treatment of VTE in specific injury patterns are reviewed. However, further evidence in the form of multi-centre, randomized controlled trials must be obtained before a standardized protocol for thromboprophylaxis in major trauma can be produced.     

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies – Adult patients

Background

Over the last decade, the treatment landscape for moderate–severe psoriasis has rapidly evolved. The Australasian College of Dermatologists sought to review and update previously published treatment goals for moderate–severe psoriasis.

Methods

A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7–9 on a 9-point scale (1 strongly disagree; 9 strongly agree).

Results

Consensus was achieved on 26/29 statements in round 1 and a further 20 statements in round 2. There was strong agreement to expanding the classification/definition of psoriasis severity by including a choice of metrics, incorporating quality of life measures, and widening the scope of high-impact sites. Consensus was also reached on revised treatment response criteria, which were then incorporated into a new treatment algorithm. There was discordance with the current requirement to undertake a trial with established systemic agents before accessing targeted therapy.

Conclusion

The ability of new targeted treatment options to change the narrative in psoriasis patient care can only be properly realised if challenges to timely and equitable access are addressed. The proposed framework for the assessment, classification and management of moderate–severe psoriasis aligns with international recommendations. Its adoption into Australian clinical practice is hoped to improve treatment outcomes and patients' satisfaction with their care.     

APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease

Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson’s disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI_95%) = 1.067–1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI_95% = 1.137–6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI_95% = 1.621–10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI_95% = 0.897–0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.     

Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8

PurposeManagement of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire.Materials and methods171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4–6 weeks, and at 2–3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as ‘vulnerable’, 11–14 as ‘intermediate’, and >14 as ‘fit’. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes.ResultsMedian follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were ‘vulnerable’, 37% were ‘intermediate’, and 12% were ‘fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001).ConclusionThe G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.