The value of the modern vascular surgeon to the health care system: A report from the Society for Vascular Surgery Valuation Work Group.

Vascular surgeons provide an important service to the health care system. They are capable of treating a wide range of disease processes that affect both the venous and arterial systems. Their presence broadens the complexity and diversity of services that a health care system can offer both in the outpatient setting and in the inpatient setting. Because of their ability to control hemorrhage, they are critical to a safe operating room environment. The vascular surgery service line has a positive impact on hospital margin through both the direct vascular profit and loss and the indirect result of assisting other surgical and medical services in providing care. The financial benefits of a vascular service line will hold true for a wide range of alternative payment models, such as bundled payments or capitation. To fully leverage a modern vascular surgeon's skill set, significant investment is required from the health care system that is, however, associated with substantial return on the investment.

The Society for Vascular Surgery Alternative Payment Model Task Force report on opportunities for value-based reimbursement in care for patients with peripheral artery disease.

The Society for Vascular Surgery Alternative Payment Model (APM) Taskforce document explores the drivers and implications for developing objective value-based reimbursement plans for the care of patients with peripheral arterial disease (PAD). The APM is a payment approach that highlights high-quality and cost-efficient care and is a financially incentivized pathway for participation in the Quality Payment Program, which aims to replace the traditional fee-for-service payment method. At present, the participation of vascular specialists in APMs is hampered owing to the absence of dedicated models. The increasing prevalence of PAD diagnosis, technological advances in therapeutic devices, and the increasing cost of care of the affected patients have financial consequences on care delivery models and population health. The document summarizes the existing measurement methods of cost, care processes, and outcomes using payor data, patient-reported outcomes, and registry participation. The document also evaluates the existing challenges in the evaluation of PAD care, including intervention overuse, treatment disparities, varied clinical presentations, and the effects of multiple comorbid conditions on the cost potentially attributable to the vascular interventionalist. Medicare reimbursement data analysis also confirmed the prolonged need for additional healthcare services after vascular interventions. The Society for Vascular Surgery proposes that a PAD APM should provide patients with comprehensive care using a longitudinal approach with integration of multiple key medical and surgical services. It should maintain appropriate access to diagnostic and therapeutic advancements and eliminate unnecessary interventions. It should also decrease the variability in care but must also consider the varying complexity of the presenting PAD conditions. Enhanced quality of care and physician innovation should be rewarded. In addition, provisions should be present within an APM for high-risk patients who carry the risk of exclusion from care because of the naturally associated high costs. Although the document demonstrates clear opportunities for quality improvement and cost savings in PAD care, continued PAD APM development requires the assessment of more granular data for accurate risk adjustment, in addition to largescale testing before public release. Collaboration between payors and physician specialty societies remains key.

Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes.

Copper (Cu) is an essential metal for bacterial physiology but in excess it is bacteriotoxic. To limit Cu levels in the cytoplasm, most bacteria possess a transcriptionally responsive system for Cu export. In the Gram-positive human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]), this system is encoded by the copYAZ operon. This study demonstrates that although the site of GAS infection represents a Cu-rich environment, inactivation of the copA Cu efflux gene does not reduce virulence in a mouse model of invasive disease. In vitro, Cu treatment leads to multiple observable phenotypes, including defects in growth and viability, decreased fermentation, inhibition of glyceraldehyde-3-phosphate dehydrogenase (GapA) activity, and misregulation of metal homeostasis, likely as a consequence of mismetalation of noncognate metal-binding sites by Cu. Surprisingly, the onset of these effects is delayed by ∼4 h even though expression of copZ is upregulated immediately upon exposure to Cu. Further biochemical investigations show that the onset of all phenotypes coincides with depletion of intracellular glutathione (GSH). Supplementation with extracellular GSH replenishes the intracellular pool of this thiol and suppresses all the observable effects of Cu treatment. These results indicate that GSH buffers excess intracellular Cu when the transcriptionally responsive Cu export system is overwhelmed. Thus, while the copYAZ operon is responsible for Cu homeostasis, GSH has a role in Cu tolerance and allows bacteria to maintain metabolism even in the presence of an excess of this metal ion.IMPORTANCE The control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it has been established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity. Glutathione, abundant in many bacteria, is known to bind Cu and has long been assumed to contribute to bacterial Cu handling. However, there is some ambiguity since neither its biosynthesis nor uptake is Cu-regulated. Furthermore, there is little experimental support for this physiological role of glutathione beyond measuring growth of glutathione-deficient mutants in the presence of Cu. Our work with group A Streptococcus provides new evidence that glutathione increases the threshold of intracellular Cu availability that can be tolerated by bacteria and thus advances fundamental understanding of bacterial Cu handling.

Analysis of English general practice level data linking medication levels, service activity and demography to levels of glycaemic control being achieved in type 2 diabetes to improve clinical practice and patient outcomes.

OBJECTIVE: Evaluate relative clinical effectiveness of treatment options for type 2 diabetes mellitus (T2DM) using a statistical model of real-world evidence within UK general practitioner practices (GPP), to quantify the opportunities for diabetes care performance improvement. METHOD: From the National Diabetes Audit in 2015-2016 and 2016-2017, GPP target glycaemic control (TGC-%HbA1c ≤58 mmol/mol) and higher glycaemic risk (HGR -%HbA1c results >86 mmol/mol) outcomes were linked using multivariate linear regression to prescribing, demographics and practice service indicators. This was carried out both cross-sectionally (XS) (within year) and longitudinally (Lo) (across years) on 35 indicators. Standardised ß coefficients were used to show relative level of impact of each factor. Improvement opportunity was calculated as impact on TGC & HGR numbers. RESULTS: Values from 6525 GPP with 2.7 million T2DM individuals were included. The cross-sectional model accounted for up to 28% TGC variance and 35% HGR variance, and the longitudinal model accounted for up to 9% TGC and 17% HGR variance. Practice service indicators including % achieving routine checks/blood pressure/cholesterol control targets were positively correlated, while demographic indicators including % younger age/social deprivation/white ethnicity were negatively correlated. The ß values for selected molecules are shown as (increased TGC; decreased HGR), canagliflozin (XS 0.07;0.145/Lo 0.04;0.07), metformin (XS 0.12;0.04/Lo -;-), sitagliptin (XS 0.06;0.02/Lo 0.10;0.06), empagliflozin (XS-;0.07/Lo 0.09;0.07), dapagliflozin (XS -;0.04/Lo -;0.4), sulphonylurea (XS -0.18;-0.12/Lo-;-) and insulin (XS-0.14;0.02/ Lo-0.09;-). Moving all GPP prescribing and interventions to the equivalent of the top performing decile of GPP could result in total patients in TGC increasing from 1.90 million to 2.14 million, and total HGR falling from 191 000 to 123 000. CONCLUSIONS: GPP using more legacy therapies such as sulphonylurea/insulin demonstrate poorer outcomes, while those applying holistic patient management/use of newer molecules demonstrate improved glycaemic outcomes. If all GPP moved service levels/prescribing to those of the top decile, both TGC/HGR could be substantially improved.

Antimicrobial activity of essential oils against multidrug-resistant clinical isolates of the Burkholderia cepacia complex.

Members of the Burkholderia cepacia complex (Bcc) are an important cause of opportunistic or nosocomial infections that may be hard to treat due to a high incidence of multidrug resistance. We characterised a collection of 51 clinical isolates from this complex, assigning them to 18 sequence types using multi-locus sequence type analysis. Resistance to eight commonly used antibiotics was assessed using by using agar-dilution assays to calculate MICs and widespread and heterogeneous multidrug resistance was confirmed, with eight strains proving resistant to all antibiotics tested. Disc diffusion screening of antimicrobial activity of a range of plant essential oils against these Bcc isolates identified six oils with significant activity (lavender, lemongrass, marjoram, peppermint, tea tree and rosewood) and broth microdilution assays indicated that of these lemongrass and rosewood oils had the highest activity, with MIC50 values of 0.5% and MIC90 values of 1%. Comparison of MIC and MBC values showed that four of these six oils, including lemongrass and rosewood, were bacteriocidal rather than bacteriostatic in their effects. Qualitative analysis of the four bacteriocidal essential oils via GC/MS indicated the presence of 55 different component compounds, mostly monoterpenes. We assessed selected essential oil components as anti-Bcc agents and demonstrated that terpinen-4-ol and geraniol were effective with MICs of 0.125-0.5% (v/v) and 0.125-1% (v/v), respectively. Time-kill studies indicate that these two alcohols are effective against non-growing cells in an efflux-dependent manner. Analysis of bacterial leakage of potassium ions and 260 nm UV-absorbing material on treatment with terpinen-4-ol and geraniol suggested that the observed anti-Bcc activity was a consequence of membrane disruption. This finding was supported by a gas chromatography analysis of bacterial fatty acid methyl esters, which indicated changes in membrane fatty acid composition caused by terpinen-4-ol and geraniol. These essential oils or oil components may ultimately prove useful as therapeutic drugs, for example to treat Bcc infections in CF patients.

Ethyl chloride spray for musculoskeletal ultrasound-guided injections: An alternative to subcutaneous injection of local anesthetic solution.

Ultrasound-guided injections such as steroid injections are common procedures involving the musculoskeletal system. They are usually performed after a subcutaneous injection of local anesthetic (LA), which can be painful. In 126 consecutive patients, local anesthesia was performed using ethyl chloride spray prior to a therapeutic ultrasound-guided injection in joints, tendons, or bursae. Ninety-nine (78.5%) patients found the use of ethyl chloride spray helpful. The use of ethyl chloride spray is an effective, patient-friendly alternative to the standard injection of local aesthetic for ultrasound-guided therapeutic musculoskeletal injections with the advantage of a lower cost of $0.18 per procedure.

Utility of selection methods for specialist medical training: A BEME (best evidence medical education) systematic review: BEME guide no. 45.

BACKGROUND: Selection into specialty training is a high-stakes and resource-intensive process. While substantial literature exists on selection into medical schools, and there are individual studies in postgraduate settings, there seems to be paucity of evidence concerning selection systems and the utility of selection tools in postgraduate training environments. AIM: To explore, analyze and synthesize the evidence related to selection into postgraduate medical specialty training. METHOD: Core bibliographic databases including PubMed; Ovid Medline; Embase, CINAHL; ERIC and PsycINFO were searched, and a total of 2640 abstracts were retrieved. After removing duplicates and screening against the inclusion criteria, 202 full papers were coded, of which 116 were included. RESULTS: Gaps in underlying selection frameworks were illuminated. Frameworks defined by locally derived selection criteria, and heavily weighed on academic parameters seem to be giving way to the evidencing of competency-based selection approaches in some settings. Regarding selection tools, we found favorable psychometric evidence for multiple mini-interviews, situational judgment tests and clinical problem-solving tests, although the bulk of evidence was mostly limited to the United Kingdom. The evidence around the robustness of curriculum vitae, letters of recommendation and personal statements was equivocal. The findings on the predictors of past performance were limited to academic criteria with paucity of long-term evaluations. The evidence around nonacademic criteria was inadequate to make an informed judgment. CONCLUSIONS: While much has been gained in understanding the utility of individual selection methods, though the evidence around many of them is equivocal, the underlying theoretical and conceptual frameworks for designing holistic and equitable selection systems are yet to be developed.

Exploring the effectiveness of couples interventions for adults living with a chronic physical illness: A systematic review.

OBJECTIVE: Partners have a significant role in a person's ability to adjust to a chronic physical illness, which warrants their inclusion in couples interventions. However to deliver more specific, tailored support it is necessary to explore which types of couples interventions are most effective across certain chronic illness populations and outcomes. METHODS: Five databases were searched using selected terms. Thirty-five articles met the eligibility criteria for inclusion. RESULTS: The majority of studies were from the US, and most interventions targeted cancer populations. Couples interventions fell into two categories according to therapeutic approach; Cognitive Behavioural Skills Training (CBST) and Relationship Counselling (RC). When compared with a patient-only intervention or controls, CBST interventions effectively targeted behavioural, physical/somatic and cognitive outcomes, while RC more effectively targeted interpersonal outcomes. CONCLUSION: Couples interventions can be more effective than patient-only interventions or controls across various patient and partner outcomes. Couples interventions tend to favour a skills-based or a relationship-based approach, which strongly influences the types outcomes effectively targeted. PRACTICE IMPLICATIONS: Our findings suggest it could be therapeutically useful to integrate these two approaches to more holistically support couples living with chronic illness. We also identify the need to target understudied illness groups and ethnicities.

Current Status of Clot Removal for Acute Pulmonary Embolism.

Acute pulmonary embolism (PE) continues to carry a high mortality if not recognized early and treated aggressively. Rapid recognition and diagnosis remains the mainstay of all efforts. Risk stratification early is paramount to guide therapy and achieve successful outcomes. Pulmonary emboli can generally be classified as massive, submassive, or stable. Fibrinolysis and/or surgical embolectomy are recommended for the treatment of the patient with massive PE to rescue the patient and restore hemodynamic stability. Current trials support an aggressive approach. In submassive PE, determination of right ventricular (RV) strain by echocardiography and biomarker assessment (troponin and B-type natriuretic peptide) identify patients who can benefit from catheter-directed therapy with the therapeutic intent of achieving a rapid reduction of RV afterload, prevention of impending hemodynamic collapse and prolonged in-hospital and outpatient survival. Current trials have not shown long-term benefit for this approach to date, and thus, this therapy should only be offered to select patients. Stable PE can be treated using both an inpatient and an outpatient approach, based on the available infrastructure. Therapy for PE continues to evolve and stratification of risks and benefits remain the key to implementation of invasive strategies.

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting.

Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

INTRODUCTION: Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. METHODS: Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. RESULTS: We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. DISCUSSION: This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety assessment.

hERG inhibitors with similar potency but different binding kinetics do not pose the same proarrhythmic risk: implications for drug safety assessment.

INTRODUCTION: Since the discovery of the link that exists between drug-induced hERG inhibition and Torsade de Pointes (TdP), extreme attention has been given to avoid new drugs inhibiting this channel. hERG inhibition is routinely screened for in new drugs and, typically, IC50 values are compared to projected plasma concentrations to define a safety margin. METHODS AND RESULTS: We aimed to show that drugs with similar hERG potency are not uniformly pro-arrhythmic-this depends on the drug binding kinetics and mode of action (trapped or not) rather than the IC50 value only. We used a mathematical model of hERG and its related encoded current IKr to simulate drug binding in different configurations. Expression systems mimicking the screening process were first investigated. hERG model was then incorporated into a canine action potential (AP) and tissue model to study the impact of drug binding configurations on AP and pseudo-ECG (QT interval prolongation). Our data show that: (1) trapped and not trapped configurations and different binding kinetics could be identified during hERG screening; (2) slow binding, not trapped drugs, induced less AP prolongation and minimal QT interval prolongation (4.7%) at a concentration equal to the IC50 whereas maximal pro-arrhythmic risk was observed for trapped drugs at the same concentration (QT interval prolongation, 23.1%). CONCLUSION: Our study demonstrates the need for screening for hERG binding configurations rather than potency alone. It also demonstrates the potential link between hERG, drug mode of action and TdP, and the need to question the current regulatory guidance.

Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore how a compound, interfering with specific ion-channel function, may explain effects at the cell-, tissue- and organ-scales. With the advent of high-throughput screening of multiple ion channels in the wet-lab, and improvements in computational modelling of their effects on cardiac cell activity, more reliable prediction of pro-arrhythmic risk is becoming possible at the earliest stages of drug development. In this paper, we review the current use of biophysically detailed mathematical models of cardiac myocyte electrical activity in drug safety testing, and suggest future directions to employ the full potential of this approach.

Enteral iron supplementation in preterm and low birth weight infants.

BACKGROUND: Preterm infants are at risk of exhausting their body iron stores much earlier than healthy term newborns. It is widespread practice to give enteral iron supplementation to preterm and low birth weight infants to prevent iron deficiency anaemia. However, it is unclear whether supplementing preterm and low birth weight infants with iron improves growth and neurodevelopment. It is suspected that excess exogenous iron can contribute to oxidative injury in preterm babies, causing or exacerbating conditions such as necrotising enterocolitis and retinopathy of prematurity. Additionally, the optimal dose and timing of commencement and cessation of iron supplementation are uncertain. OBJECTIVES: To evaluate the effect of prophylactic enteral iron supplementation on growth and neurodevelopmental outcomes in preterm and low birth weight infants. The secondary objectives were to determine whether iron supplementation results in improved haematological parameters and prevents other causes of morbidity and mortality. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (1951 to August 2011), CINAHL (1982 to August 2011) and conference proceedings and previous reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials that compared enteral iron supplementation with no iron supplementation, or different regimens of enteral iron supplementation in preterm or low birth weight infants or both. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group. Both review authors separately evaluated trial quality and data extraction. We synthesised data using risk ratios (RRs), risk differences (RDs) and weighted mean differences (WMDs). Where data about the methodology and results or both were lacking, we made an attempt to contact the study authors for further information. MAIN RESULTS: We included twenty-six studies (2726 infants) in the analysis. The heterogeneity of participants, methods and results precluded an extensive quantitative synthesis. Of the 21 studies comparing iron supplementation with controls, none evaluated neurodevelopmental status as an outcome. Of thirteen studies reporting at least one growth parameter as an outcome, only one study of poor quality found a significant benefit of iron supplementation. Regarding haematological outcomes, no benefit for iron supplementation was demonstrated within the first 8.5 weeks of postnatal life (16 trials), except by two poor quality studies. After this age, most studies reported a higher mean haemoglobin in iron-supplemented infants. We were only able to include a limited number of studies in a quantitative meta-analysis, which suggested the haemoglobin concentration in iron-supplemented infants was higher by about 6 g/L at six to nine months. One study comparing high dose and low dose iron supplementation monitored neurodevelopmental outcome for one year, without finding any significant difference between the groups. One study comparing early versus late commencement of iron supplementation found no difference in cognitive outcome, but an increased rate of abnormal neurological examination in the late iron group at five years of age. The studies comparing high and low doses of iron indicated that there was no discernible haematological benefit in exceeding 'standard' doses of iron (i.e. 2 mg/kg/day to 3 mg/kg/day). AUTHORS' CONCLUSIONS: The available data suggest that infants who receive iron supplementation have a slightly higher haemoglobin level, improved iron stores and a lower risk of developing iron deficiency anaemia when compared with those who are unsupplemented. However, it is unclear whether iron supplementation in preterm and low birth weight infants has long term benefits in terms of neurodevelopmental outcome and growth. The optimum timing and duration of iron supplementation remains unclear.

Acute Aortic Treatment Center.

Acute aortic syndromes are a life-threatening set of conditions that require rapid triage and intervention to obtain satisfactory outcomes. The Methodist Hospital is the first institution to establish an Acute Aortic Treatment Center (AATC) based on a clinical care pathway that expedites the care of acute aortic syndromes. This pathway has resulted in a 64% reduction in time to definitive therapy and a reduction in intensive care unit (ICU) length of stay. Establishment of a multidisciplinary pathway to treat acute aortic syndromes improves efficiency and enhances outcomes.

Outcomes before and after initiation of an acute aortic treatment center.

BACKGROUND: Acute aortic syndromes remain life-threatening. Time is of the essence, as mortality rises with increasing time after the acute episode. The aim of this report is to show changes in practice and outcomes after the establishment of an acute aortic treatment center (AATC) to expedite the care of acute aortic syndromes in a major metropolitan area with the belief that "door to intervention time under 90 minutes" reduces mortality and morbidity from acute aortic disease. METHODS: A database of patients admitted with acute aortic disease (Type A and B aortic dissections, acute thoraco-abdominal aortic aneurysms, acute and ruptured abdominal aortic aneurysms) for 1 year prior to initiation (2007) and 1 year after initiation of the pathway (AATC) in 2008 was developed. Comorbidities were scored according to Society of Vascular Surgery criteria. Anatomic and functional outcomes were determined and categorized by Society of Vascular Surgery reporting criteria. Multivariate analysis was performed for categorical outcomes and Cox proportional hazard analyses for time-dependent outcomes. RESULTS: Six hundred twenty-one patients reported with aortic disease to the cardiovascular services; 306 patients were considered to have acute disease. When compared with the year before the AATC was instituted, there was a 30% increase in the total number of admissions and a 25% increase in acute pathology after setting up the AATC (P = .02). There was a two-fold increase in thoracic aortic dissections admitted to the service. Initiation of the treatment pathway resulted in a highly significant 64% reduction in time to definitive therapy (526 ± 557 vs 187 ± 258 minutes, mean ± SD pre-AATC vs AATC; P = .0001). Comorbidity scores were equivalent between the two cohorts. Despite the increase in acuity, mortality (4% vs 6%) and morbidity (41% vs 45%) rates were unchanged, and there was a significant decrease in intensive care unit length of stay (5 vs 4 days, pre-AATC cohort vs the AATC cohort), but total hospital length of stay (11 vs 10 days) was unchanged. There was no correlation between deaths within 30 days and length of stay in the intensive care unit. CONCLUSION: Establishment of a multidisciplinary AATC pathway was associated with a 30% increase in volume, 64% reduction in time to definitive treatment, improved throughput with reduced intensive care unit time, and maintained clinical efficacy despite an increase in acute admissions. These results suggest the concept be further evaluated.

Combined endoscopic approach for the management of a difficult recto-sigmoid anastomotic stricture.

A 48-year-old woman underwent an emergency laparotomy for a perforated diverticular abscess. At operation, a peritoneal lavage was carried out, but no colonic resection was undertaken. Subsequently, she developed recurrent sepsis and underwent a second laparotomy. The patient was referred to our institution for a definitive left hemicolectomy and diverting loop colostomy. Before closing the colostomy, a contrast enema revealed obstruction of the lumen at the anastomotic site. This was refractory to conventional colonoscopic dilatation. A simultaneous endoscope was passed through the distal loop of the colostomy in addition to a conventional approach. A defect was created that allowed passage of a guide-wire and balloon dilator. One week later, the anastomosis remained patent, and the colostomy closed. The patient remains well, with normal bowel function. This novel combined endoscopic approach for dealing with colonic stenoses avoids the higher morbidity and mortality associated with an open surgical procedure.

Identification and assessment of new vaccine candidates for group A streptococcal infections.

Group A Streptococcus (GAS) is a human-specific pathogen responsible for a wide variety of human diseases. Numerous GAS surface antigens interact with the human immune system and only some of these proteins have been studied in depth. A few of these may elicit protective response against GAS infection. In this study, we have used an in silico approach to identify antigenic peptides from GAS surface proteins. Putative GAS surface proteins from the M1 GAS genome were identified by the presence on LPxTG cell-wall anchoring motif and an export signal sequence. This technique identified 17 proteins of known or putative function, and another 11 which do not have known homologues. Peptides derived from predicted antigenic sequences near the amino terminus of six of these proteins, and another seven peptides derived from the two known surface proteins, GRAB and MtsA, were conjugated to keyhole lymphocyanin (KLH), and investigated for their capacity to induce opsonic antibody responses in outbred Quackenbush mice. All peptide-KLH antisera demonstrated opsonic capacity against both 88/30 and M1 GAS. However, KLH sera alone was also able to induce opsonic antibodies, suggesting that anti-KLH antibodies contributed to the opsonisation seen in the peptide-KLH antisera. KLH is therefore a promising carrier molecule for potential GAS peptide vaccines.

The comprehensiveness care of sickle cell disease.

Millions of people across the world have sickle cell disease (SCD). Although the true prevalence of SCD in Europe is not certain, London (UK) alone had an estimated 9000 people with the disorder in 1997. People affected by SCD are best managed by a multidisciplinary team of professionals who deliver comprehensive care: a model of healthcare based on interaction of medical and non-medical services with the affected persons. The components of comprehensive care include patient/parent information, genetic counselling, social services, prevention of infections, dietary advice and supplementation, psychotherapy, renal and other specialist medical care, maternal and child health, orthopaedic and general surgery, pain control, physiotherapy, dental and eye care, drug dependency services and specialist sickle cell nursing. The traditional role of haematologists remains to co-ordinate overall management and liase with other specialities as necessary. Co-operation from the affected persons is indispensable to the delivery of comprehensive care. Working in partnership with the hospital or community health service administration and voluntary agencies enhances the success of the multidisciplinary team. Holistic care improves the quality of life of people affected by SCD, and reduces the number as well as length of hospital admissions. Disease-related morbidity is reduced by early detection and treatment of chronic complications. Comprehensive care promotes awareness of SCD among affected persons who are encouraged to take greater control of their own lives, and achieves better patient management than the solo efforts of any single group of professionals. This cost-effective model of care is an option for taking haemoglobinopathy services forward in the new millennium.