The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

A review of sedation scales for the cardiac catheterization laboratory

Sedation scales have the potential to facilitate effective procedural sedation and analgesia in the cardiac catheterization laboratory (CCL). For this potential to become realised, a scale that is suitable for use in the CCL either needs to be identified or developed. To identify sedation scales, a review of Medline and CINHAL was conducted. One sedation scale for the CCL, the NASPE SED, and 15 Intensive Care Unit (ICU) scales met the inclusion and exclusion criteria. Analysis of the scale’s item structures and psychometric properties was then performed. None of these scales were deemed suitable for use in the CCL. As such, further research is required to develop a new scale. The new scale should consist of more than one item because it will be the most effective for tracking the patient’s response to medications. Specific tests required to conduct a rigorous evaluation of the new scale’s psychometric properties are outlined in this paper.

Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Fever management in children : Vietnamese parents' and paediatric nurses' knowledge, beliefs and practices

This thesis comprised two studies: an exploratory study and a cross-sectional survey, guided by the Theory of Planned Behaviour. It explored parents' and paediatric nurses' knowledge, beliefs and practices about fever management in Vietnam. The research highlights the determinants of parents' and nurses' intentions to manage childhood fever which can be targeted for future interventions to integrate latest evidence-based practices.

A retrospective cohort study of Acticoat™ versus Silvazine™ in a paediatric population

We wished to determine whether changing our centre's practice of using Acticoat instead of Silvazine as our first-line burns dressing provided a better standard of care in terms of efficacy, cost and ease of use. A retrospective cohort study was performed examining 328 Silvazine treated patients from January 2000 to June 2001 and 241 Acticoat treated patients from July 2002 to July 2003. During those periods the respective dressings were used exclusively. There was no significant difference in age, %BSA and mechanism of burn between the groups. In the Silvazine group, 25.6% of children required grafting compared to 15.4% in the Acticoat group (p=0.001). When patients requiring grafting were excluded, the time taken for re-epithelialisation in the Acticoat group (14.9 days) was significantly less than that for the Silvazine group (18.3 days), p=0.047. There were more wounds requiring long term scar management in the Silvazine group (32.6%) compared to the Acticoat group (29.5%), however this was not significant. There was only one positive blood culture in each group, indicating that both Silvazine and Acticoat are potent antimicrobial agents. The use of Acticoat as our primary burns dressing has dramatically changed our clinical practice. Inpatients are now only 18% of the total admissions, with the vast majority of patients treated on an outpatient basis. In terms of cost, Acticoat was demonstrated to be less expensive over the treatment period than Silvazine . We have concluded that Acticoat is a safe, cost-effective, efficacious dressing that reduces the time for re-epithelialisation and the requirement for grafting and long term scar management, compared to Silvazine.

Cataract surgery in eyes with low corneal astigmatism : implantation of the AcrySof IQ Toric SN6AT2 intraocular lens

Purpose The aim of this study is to assess the refractive and visual outcomes following cataract surgery and implantation of the AcrySof IQ Toric SN6AT2 intraolcular lens (IOL) (Alcon Laboratories, Inc) in patients with low corneal astigmatism. Materials and Methods A retrospective, consecutive, single surgeon series of ninety-eight eyes of 88 patients following cataract surgery and implantation of the AcrySof IQ Toric SN6AT2 IOL in eyes with low preoperative corneal astigmatism. Postoperative measurements were obtained at one month post surgery. Main outcome measures were monocular distance visual acuity and residual refractive astigmatism. Results The mean preoperative corneal astigmatic power vector (APV) was 0.38 ± 0.09 D. Following surgery and implantation of the toric IOL, mean postoperative refractive APV was 0.13 ± 0.10 D. Mean postoperative distance uncorrected visual acuity (UCVA) was 0.08 ± 0.09 logMAR. Postoperative spherical equivalent refraction (SER) resulted in a mean of - 0.23 ± 0.22 D, with 96% of eyes falling within 0.50 D of the target SER. Conclusions The AcrySof IQ Toric SN6AT2 IOL is a safe and effective option for eyes undergoing cataract surgery with low amounts of preoperative corneal astigmatism.

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

Extreme temperatures and paediatric emergency department admissions

Background Children are particularly vulnerable to the effects of extreme temperatures. Objective To examine the relationship between extreme temperatures and paediatric emergency department admissions (EDAs) in Brisbane, Australia, during 2003–2009. Methods A quasi-Poisson generalised linear model combined with a distributed lag non-linear model was used to examine the relationships between extreme temperatures and age-, gender- and cause-specific paediatric EDAs, while controlling for air pollution, relative humidity, day of the week, influenza epidemics, public holiday, season and long-term trends. The model residuals were checked to identify whether there was an added effect due to heat waves or cold spells. Results There were 131 249 EDAs among children during the study period. Both high (RR=1.27; 95% CI 1.12 to 1.44) and low (RR=1.81; 95% CI 1.66 to 1.97) temperatures were significantly associated with an increase in paediatric EDAs in Brisbane. Male children were more vulnerable to temperature effects. Children aged 0–4 years were more vulnerable to heat effects and children aged 10–14 years were more sensitive to both hot and cold effects. High temperatures had a significant impact on several paediatric diseases, including intestinal infectious diseases, respiratory diseases, endocrine, nutritional and metabolic diseases, nervous system diseases and chronic lower respiratory diseases. Low temperatures were significantly associated with intestinal infectious diseases, respiratory diseases and endocrine, nutritional and metabolic diseases. An added effect of heat waves on childhood chronic lower respiratory diseases was seen, but no added effect of cold spells was found. Conclusions As climate change continues, children are at particular risk of a variety of diseases which might be triggered by extremely high temperatures. This study suggests that preventing the effects of extreme temperature on children with respiratory diseases might reduce the number of EDAs.

Validation of a parent-proxy quality of life questionnaire for paediatric chronic cough (PC-QOL)

Background Quality of life (QOL) measures are an important patient-relevant outcome measure for clinical studies. Currently there is no fully validated cough-specific QOL measure for paediatrics. The objective of this study was to validate a cough-specific QOL questionnaire for paediatric use. Method 43 children (28 males, 15 females; median age 29 months, IQR 20–41 months) newly referred for chronic cough participated. One parent of each child completed the 27-item Parent Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough-related measures (visual analogue score and verbal category descriptive score) on two occasions separated by 2–3 weeks. Cough counts were also objectively measured on both occasions. Results Internal consistency for both the domains and total PC-QOL at both test times was excellent (Cronbach alpha range 0.70–0.97). Evidence for repeatability and criterion validity was established, with significant correlations over time and significant relationships with the cough measures. The PC-QOL was sensitive to change across the test times and these changes were significantly related to changes in cough measures (PC-QOL with: verbal category descriptive score, rs=−0.37, p=0.016; visual analogue score, rs=−0.47, p=0.003). Significant correlations of the difference scores for the social domain of the PC-QOL and the domain and total scores of the PedsQL were also noted (rs=0.46, p=0.034). Conclusion The PC-QOL is a reliable and valid outcome measure that assesses QOL related to childhood cough at a given time point and measures changes in cough-specific QOL over time.

Functional independence following subacute inpatient rehabilitation was not affected by age among older patients recovering from cardiac-related hospital admissions

Introduction Older people recovering from cardiac events requiring an acute hospital admission may experience a decline in physical function limiting their ability to return home to their previous accommodation. Subacute inpatient rehabilitation therapies have potential to assist recovery of physical functioning. However, it is unknown whether age influences the length of stay or physical functioning at discharge from subacute inpatient rehabilitation for this population. Objectives This study examined the outcomes of a cohort of older patients recovering from a cardiac event requiring hospitalisation to investigate the association between age and physical function at discharge, as well as age and length of rehabilitation stay. Methods Participants included 145 consecutive inpatient admissions to a subacute geriatric assessment and rehabilitation unit with a cardiac condition as their primary reason for hospital admission. Participants were required to complete a multi-disciplinary physical functioning assessment within 72 hours of admission to the unit, and again within 72 hours prior to discharge from the unit. The primary outcome measure was the Functional Independence Measure motor score. Demographic and clinical information, including length of stay and discharge destination, were also recorded. Results A total n=126 (87%) participants, with a mean (standard deviation) age of 79 (10) years, had both assessments completed and were included in analyses. Participants who had passed away (n=4, 3%), or did not have both assessments completed per protocol were excluded from analyses. Discharge destinations included home (n=101, 80%), residential aged care (n=17, 13%) and another hospital (n=8, 6%). The (median, interquartile range) Functional Independence Measure motor score was higher at discharge (79, 71 to 84) than admission (61, 48 to 71); z=7.75 p<0.001. Age was not associated with Functional Independence Measure motor score at discharge (t= -0.18, p=0.86), or length of stay in the rehabilitation unit (t= -0.52, 0.60). Conclusion Any perception that age may be associated with longer lengths of stay and reduced physical function outcomes among patients with cardiac conditions admitted for subacute inpatient rehabilitation for older adults is not supported data from this investigation. Older age should not be considered a disincentive when considering the suitability of patients with cardiac diagnoses for this type of inpatient rehabilitation or their potential physical functioning outcome.

Liability in negligence and the failure to disclose multiple risks in surgery : I would have been willing to run the risk

It has been 21 years since the decision in Rogers v Whitaker and the legal principles concerning informed consent and liability for negligence are still strongly grounded in this landmark High Court decision. This paper considers more recent developments in the law concerning the failure to disclose inherent risks in medical procedures, focusing on the decision in Wallace v Kam [2013] HCA 19. In this case, the appellant underwent a surgical procedure that carried a number of risks. The surgery itself was not performed in a sub-standard way, but the surgeon failed to disclose two risks to the patient, a failure that constituted a breach of the surgeon’s duty of care in negligence. One of the undisclosed risks was considered to be less serious than the other, and this lesser risk eventuated causing injury to the appellant. The more serious risk did not eventuate, but the appellant argued that if the more serious risk had been disclosed, he would have avoided his injuries completely because he would have refused to undergo the procedure. Liability was disputed by the surgeon, with particular reference to causation principles. The High Court of Australia held that the appellant should not be compensated for harm that resulted from a risk he would have been willing to run. We examine the policy reasons underpinning the law of negligence in this specific context and consider some of the issues raised by this unusual case. We question whether some of the judicial reasoning adopted in this case, represents a significant shift in traditional causation principles.