Laparoscopic Appendectomy in Italy: An Appraisal of 26,863 Cases

Objective: To evaluate the practice of laparoscopic appendectomy (LA) in Italy. Methods: On behalf of the Italian Society of Young Surgeons (SPIGC), an audit of LA was carried out through a written questionnaire sent to 800 institutions in Italy. The questions concerned the diffusion of laparoscopic surgery and LA over the period 1990 through 2001, surgery-related morbidity and mortality rates, indications for LA, the diagnostic algorithm adopted prior to surgery, and use of LA among young surgeons (<40 years). Results: A total of 182 institutions (22.7%) participated in the current audit, and accounted for a total number of 26863 LA. Laparoscopic surgery is performed in 173 (95%) institutions, with 144 (83.2%) routinely performing LA. The mean interval from introduction of laparoscopic surgery to inception of LA was 3.4 ± 2.5 years. There was an emergent basis for 8809 (32.8%) LA procedures (<6 hours of admission); 10314 (38.4%) procedures were performed on an urgent basis (<24 hours of admission); while 7740 (28.8%) procedures were elective. The conversion rate was 2.1% (561 cases) and was due to intraoperative complications in 197 cases (35.1%). Intraoperative complications ranged as high as 0.32%, while postoperative complications were reported in 1.2% of successfully completed LA. The mean hospital stay for successfully completed LA was 2.5 ± 1.05 days. The highest rate of intraoperative complications was reported as occurring during the learning curve phase of their experience (in their first 10 procedures) by 39.7% of the surgeons. LA was indicated for every case of suspected acute appendiceal disease by 51.8% of surgeons, and 44.8% order abdominal ultrasound (US) prior to surgery. A gynecologic counseling is deemed necessary only by 34.5% surgeons, while an abdominal CT scan is required only by 1.5%. The procedure is completed laparoscopically in the absence of gross appendiceal inflammation by 83%; 79.8% try to complete the procedure laparoscopically in the presence of concomitant disease; while 10.4% convert to open surgery in cases of suspected malignancy. Of responding surgeons aged under 40, 76.3% can perform LA, compared to 47.3% surgeons of all age categories. Conclusions: The low response rate of the present survey does not allow us to assess the diffusion of LA in Italy, but rather to appraise its practice in centers routinely performing laparoscopic surgery. In the hands of experienced surgeons, LA has morbidity rates comparable to those of international series. The higher diagnostic yield of laparoscopy makes it an invaluable tool in the management algorithm of women of childbearing age; its advantages in the presence of severe peritonitis are less clear-cut. Surgeons remain the main limiting factor preventing a wider diffusion of LA in our country, since only 47.3% of surgeons from the audited institutions can perform LA on a routine basis.

Reducing the incidence of coronary heart disease

The incidence of coronary heart disease (CHD) has been significantly reduced by the introduction of the National Service Framework in 2000 but has not yet reached set targets. This article analyses the adverse effects of specific CHD risk factors to the cardiovascular system and proposes local and national strategies for further reduction in the incidence, morbidity and mortality of CHD. It provides an example of how nurses can use a health promotion programme to support patients in giving up smoking, a major contributing factor in CHD. The programme uses cognitive behaviour therapy to improve patients' uptake and adherence.

Improving the quality of life for patients with angina pectoris: a team approach to disease management.

The evaluation of outcome of management of angina patients is now inextricably linked with an assessment of quality of life. Angina, as a manifestation of coronary heart disease, is a major cause of morbidity and mortality in many countries. Optimal management of patients with angina is of undeniable national and global significance.

This paper attempts to indicate the importance of a team approach and the implications for patients’ quality of life of involving professionals with a variety of different skills. It outlines current guidelines for the management of angina, including aspects of diagnosis, treatment and rehabilitation. Factors of relevance to the management of patients as individuals are discussed. The association of improved quality of life and reduced severity of symptoms with benefit for both the individual and society is considered.

Differential Pharmacokinetics of Digoxin in Elderly Patients

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.
For over 200 years debate has raged regarding the use of digitalis glycosides in cardiac disease. At present digoxin is the most commonly prescribed digitalis compound. This review describes the pharmacokinetics of digoxin and in particular how they are altered with increasing age. When considering the elderly population it is important to recognise the heterogeneity of response in this group, therefore there are no rules, with regards to prescribing, that can apply to the entire elderly population.

Routine delirium monitoring in a UK critical care unit

Introduction Delirium in the intensive care unit (ICU) is associated with increased morbidity and mortality. Using an assessment tool has been shown to improve the ability of clinicians in the ICU to detect delirium. The confusion assessment method for the ICU (CAM-ICU) is a validated delirium-screening tool for critically ill intubated patients. The aim of this project was to establish the feasibility of routine delirium screening using the CAM-ICU and to identify the incidence of delirium in a UK critical care unit.

Development of a novel PCR assay for the identification of the black yeast, Exophiala (Wangiella) dermatitidis from adult patients with cystic fibrosis (CF)

Cystic fibrosis (CF) patients may suffer increased morbidity and mortality through colonisation, allergy and invasive infection from fungi. The black yeast, Exophiala dermatitidis (synonym Wangiella dermatitidis) has been found with increasing frequency in sputum specimens of CF patients, with reported isolation rates ranging from 1.1 to 15.7%. At present, no diagnostic PCR exists to aid with the clinical laboratory detection and identification of this organism. A novel species-specific PCR-based assay was developed for the detection of E. dermatitidis, based on employment of rDNA operons and interspacer (ITS) regions between these rDNA operons. Two novel primers, (designated ExdF & ExdR) were designed in silico with the aid of computer-aided alignment software and with the alignment of multiple species of Exophiala, as well as with other commonly described yeasts and filamentous fungi within CF sputum, including Candida. Aspergillus and Scedosporium. An amplicon of approximately 455 by was generated, spanning the partial ITS I region - the complete 5.8S rDNA region - partial ITS2 region, employing ExdF (forward primer [16-mer], 5'-CCG CCT ATT CAG GTC C-3' and ExdR (reverse primer [16-mer], 5'-TCT CTC CCA CTC CCG C-3', was employed and optimised on extracted genomic DNA from a well characterised culture of E. dermatitidis, as well as with high quality genomic DNA template from a further 16 unrelated fungi, including Candida albicans, C. dubliniensis, C. parapsilosis, C. glabrata, Scedosporium apiospermum, Penicillium sp., Aspergillus fumigatus, Aspergillus versicolor, Pichia guilliermondii, Rhodotorula sp., Trichosporon sp., Aureobasidium pullulans, Fusarium sp., Mucor hiemalis, Bionectria ochroleuca, Gibberella pulicaris. Results demonstrated that only DNA from E. dermatitidis gave an amplification product of the expected sire, whilst none of the other fungi were amplifiable. Subsequent employment of this primer pair detected this yeast from mycological cultures from 2/50 (4%) adult CF patients. These two patients were the only patients who were previously shown to have a cultural history of E. dermatitidis from their sputum. E. dermatitidis is a slow-growing fungus, which usually takes up to two weeks to culture in the microbiology laboratory and therefore is slow to detect conventionally, with the risk of bacterial overgrowth from common co-habiting pan- and multiresistant bacterial pathogens from sputum. namely Pseudomonas aeruginosa and Burkholderia cepacia complex organisms, hence this species-specific PCR assay may help detect this organism from CF sputum more specifically and rapidly. Overall, employment of this novel assay nay help in the understanding of the occurrence. aetiology and epidemiology of E. dermatitidis, as an emerging fungal agent in patients with CF. (C) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A national survey of the mangement of delirium in UK intensive care units

Background: Delirium is an acute organ dysfunction common amongst patients treated in intensive care units. The associated morbidity and mortality are known to be substantial. Previous surveys have described which screening tools are used to diagnose delirium and which medications are used to treat delirium, but these data are not available for the United Kingdom. Aim: This survey aimed to describe the UK management of delirium by consultant intensivists. Additionally, knowledge and attitudes towards management of delirium were sought. The results will inform future research in this area. Methods: A national postal survey of members of the UK Intensive Care Society was performed. A concise two page questionnaire survey was sent, with a second round of surveys sent to non-respondents after 6 weeks. The questionnaire was in tick-box format. Results: Six hundred and eighty-one replies were received from 1308 questionnaires sent, giving a response rate of 52%. Twenty-five percent of respondents routinely screen for delirium, but of these only 55% use a screening tool validated for use in intensive care. The majority (80%) of those using a validated instrument used the Confusion Assessment Method for the Intensive Care Unit. Hyperactive delirium is treated pharmacologically by 95%; hypoactive delirium is treated pharmacologically by 25%, with haloperidol the most common agent used in both. Over 80% of respondents agreed that delirium prolongs mechanical ventilation and hospital stay and requires active treatment. Conclusions: This UK survey demonstrates screening for delirium is sporadic. Pharmacological treatment is usually with haloperidol in spite of the limited evidence to support this practice. Hypoactive delirium is infrequently treated pharmacologically.

Respiratory syncytial virus (RSV) vaccines - Two steps back for one leap forward

Respiratory viruses are among the most important causes of morbidity and mortality worldwide. From a vaccine viewpoint, such viruses may be divided into two principle groups-those where infection results in long-term immunity and whose continued survival requires constant mutation, and those where infection induces incomplete immunity and repeated infections are common, even with little or no mutation. Influenza virus and respiratory syncytial virus (RSV) typify the former and latter groups, respectively. Importantly, successful vaccines have been developed against influenza virus. However, this is not the case for RSV, despite many decades of research and several vaccine approaches. Similar to natural infection, the principle limitation of candidate RSV vaccines in humans is limited immunogenicity, characterised in part by short-term RSV-specific adaptive immunity. The specific reasons why natural RSV infection is insufficiently immunogenic in humans are unknown but circumvention of innate and adaptive immune responses are likely causes. Fundamental questions concerning RSV/host interactions remain to be addressed at both the innate and adaptive immune levels in humans in order to elucidate mechanisms of immune response circumvention. Taking the necessary steps back to generate such knowledge will provide the means to leap forward in our quest for a successful RSV vaccine. Recent developments relating to some of these questions are discussed. (C) 2007 Elsevier B.V. All rights reserved.

Association of Genetic Variants at 3q22 with Nephropathy in Patients with Type 1 Diabetes Mellitus

Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also been reported earlier by several other groups. To fine map this locus, we conducted a multistage case-control association study in T1DM patients, comprising 1822 cases with nephropathy and 1874 T1DM patients free of nephropathy, from Finland, Iceland, and the British Isles. At the screening stage, we genotyped 3072 tag SNPs, spanning a 28 Mb region, in 234 patients and 215 controls from Finland. SNPs that met the significance threshold of p

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10 -5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10 -5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10 -10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Transfusion in the management of patients with megaloblastic anaemia

Transfusion has been associated with significant morbidity and mortality in megaloblastic anaemia (MA). This retrospective study was undertaken to examine the usefulness of transfusion in the management of MA. Fifty-two patients with MA were identified. Of the 20 transfused patients 13 were treated with diuretics and six with potassium supplements. The mean haemoglobin (Hb) of the transfused group was 6.5 g/dl (range 4.8-10.4 g/dl), and of the 32 non-transfused patients 10.5 g/dl (range 5.6-17.0 g/dl). The Hb and packed cell volume (PCV) were significantly lower in the transfused group. Only two of 32 non-transfused group were given potassium supplements. In this small group of patients with MA, transfusion appeared to be safe and no complications of transfusion were identified. However, advice was not being followed. We would suggest that, although transfusion has a minor role in the management of MA, consideration must be given to the general hazards of transfusion.

Identification of essential operons with a rhamnose-inducible promoter in Burkholderia cenocepacia

Scanning of bacterial genomes to identify essential genes is of biological interest, for understanding the basic functions required for life, and of practical interest, for the identification of novel targets for new antimicrobial therapies. In particular, the lack of efficacious antimicrobial treatments for infections caused by the Burkholderia cepacia complex is causing high morbidity and mortality of cystic fibrosis patients and of patients with nosocomial infections. Here, we present a method based on delivery of the tightly regulated rhamnose-inducible promoter P(rhaB) for identifying essential genes and operons in Burkholderia cenocepacia. We demonstrate that different levels of gene expression can be achieved by using two vectors that deliver P(rhaB) at two different distances from the site of insertion. One of these vectors places P(rhaB) at the site of transposon insertion, while the other incorporates the enhanced green fluorescent protein gene (e-gfp) downstream from P(rhaB). This system allows us to identify essential genes and operons in B. cenocepacia and provides a new tool for systematically identifying and functionally characterizing essential genes at the genomic level.

An expression vector containing a rhamnose-inducible promoter provides tightly regulated gene expression in Burkholderia cenocepacia

Infection of the respiratory tract caused by Burkholderia cepacia complex poses a serious risk for cystic fibrosis (CF) patients due to the high morbidity and mortality associated with the chronic infection and the lack of efficacious antimicrobial treatments. A detailed understanding of the pathogenicity of B. cepacia complex infections is hampered in part by the limited availability of genetic tools and the inherent resistance of these isolates to the most common antibiotics used for genetic selection. In this study, we report the construction of an expression vector which uses the rhamnose-regulated P(rhaB) promoter of Escherichia coli. The functionality of the vector was assessed by expressing the enhanced green fluorescent protein (eGFP) gene (e-gfp) and determining the levels of fluorescence emission. These experiments demonstrated that P(rhaB) is responsive to low concentrations of rhamnose and it can be effectively repressed with 0.2% glucose. We also demonstrate that the tight regulation of gene expression by P(rhaB) promoter allows us to extend the capabilities of this vector to the identification of essential genes.

Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci in Finnish, Danish and French T1D families.

Plasma glutathione peroxidase activity is reduced in haemodialysis patients

Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was to assess the activity of eGPX in patients with end-stage renal failure on haemodialysis. Venous blood was collected from 87 haemodialysis patients immediately prior to and after dialysis and from 70 healthy controls. Serum eGPX activity was measured using hydrogen peroxide as substrate and immunoreactivity determined by ELISA. eGPX activity was significantly reduced in dialysis patients when compared to controls (106 +/- 2.7 and 281 +/- 3.6 U/l respectively, p <0.001). Following haemodialysis, eGPX activity rose significantly to 146 +/- 3.8 U/l, p <0.001, although remaining below control values (p <0.005). Immunoreactive eGPX, however, was similar in all groups (pre-dialysis 14.10 +/- 1.26 microg/ml, post-dialysis 14.58 +/- 1.35 microg/ml, controls 15.20 +/- 1.62 microg/ml, p = NS). A decrease was observed in the specific activity of eGPX in patients when compared to controls (8.81 +/- 1.14, 10.71 +/- 1.54 and 21.97 +/- 1.68 U/mg respectively, p <0.0001). eGPX activity is impaired in patients undergoing haemodialysis and so may contribute to atherogenesis in renal failure.