An update on cardiac implantable electronic devices for the general physician.

Cardiac electronic device implantation is a common and important intervention for patients with tachy-and bradyarrhythmia. An increasing number of patients are receiving more complex devices such as cardiac resynchronisation therapy or devices with a defibrillation function. Over the last 5 years, two new models of cardiac device have emerged, subcutaneous defibrillators and leadless pacemakers. With an ageing population and data demonstrating 2000 per 100,000 of the population aged over 75 years have a cardiac device, it is essential that the general physician remains updated on the common pacemaker indications and available therapies.

Effects of hyperaemia on left ventricular longitudinal strain in patients with suspected coronary artery disease : A first-pass stress perfusion cardiovascular magnetic resonance imaging study.

AIMS: Myocardial perfusion imaging during hyperaemic stress is commonly used to detect coronary artery disease. The aim of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E') and late diastolic velocities (A') with adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: 44 patients met the inclusion criteria and underwent CMR imaging. The CMR imaging protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. Rest and stress HLA cine CMR images were analysed using feature-tracking software for the assessment of myocardial deformation. The presence of perfusion defects was scored on a binomial scale. In patients with hyperaemia-induced perfusion defects, rest global longitudinal strain GLS (-16.9 ± 3.7 vs. -19.6 ± 3.4; p-value = 0.02), E' (-86 ± 22 vs. -109 ± 38; p-value = 0.02), GLSR (69 ± 31 vs. 93 ± 38; p-value = 0.01) and stress GLS (-16.5 ± 4 vs. -21 ± 3.1; p < 0.001) were significantly reduced when compared with patients with no perfusion defects. Stress GLS was the strongest independent predictor of perfusion defects (odds ratio 1.43 95% confidence interval 1.14-1.78, p-value <0.001). A threshold of -19.8% for stress GLS demonstrated 78% sensitivity and 73% specificity for the presence of hyperaemia-induced perfusion defects. CONCLUSIONS: At peak myocardial hyperaemic stress, GLS is reduced in the presence of a perfusion defect in patients with suspected coronary artery disease. This reduction is most likely caused by reduced endocardial blood flow at maximal hyperaemia because of transmural redistribution of blood flow in the presence of significant coronary stenosis.

Shaping the future of our training.

The Shape of Training Review proposed fundamental changes to the nature and delivery of medical training in the UK. In part this is to respond to the increasing care needs of our ageing population and importantly to address problems within the current system of medical training. Concerns have been raised by trainees over the process and outcome of the Review, and the RCPE's Trainees & Members' Committee has worked to ensure that the views and experiences of medical trainees from across the UK have been represented. This Perspective provides an overview of the proposals, our concerns about the process and a summary of ongoing work to address these issues.

Clinician referrals for stress echocardiography: are we compliant with the NICE guidelines?

Accurate diagnosis of stable angina is of paramount importance, and where possible, this should be based on clinical history. In cases of uncertainty, the National Institute for Health and Care Excellence (NICE) provides a framework for assisting diagnosis based on pre-test likelihood (PTL) of coronary artery disease. Functional testing such as stress echocardiography (SE) is recommended as a first-line investigation in patients with PTL of 30-60%. This study evaluated hospital clinicians' adherence to this recommendation. A prospective analysis of patients referred for SE at a district general hospital between March and May 2013 was performed. Data were extracted from an electronic database of SE reports and medical notes. A total of 193 patients were assessed. The most common PTL was 61-90%, accounting for 40% of the cohort. Of them, 14% had a PTL of 30-60%. Of these, 15% had positive SE; 57% described non-anginal pain, as defined by NICE, of whom only nine cases had SE positivity. None of these patients required revascularisation. Findings suggest that SE is being used in a much broader selection group than advocated by NICE. This may often be for its exclusion value rather than to stratify risk. Although utility may be justified in high-risk patients to avoid proceeding directly to invasive angiography, SE appears to add little in those with non-anginal pain and with low PTL. Greater focus should be directed towards characterisation of symptoms, which may negate the need for subsequent investigation.

Oxygen use for chest pain in coronary care units across the UK.

AIM: To quantify the adherence to national guidance for the use of oxygen in patients presenting with chest pain to coronary care units (CCUs) across the UK. DESIGN: Prospective survey. METHODS: A total of 307 hospitals were contacted by telephone between August 2010 and October 2010. Of these, 48 had no CCUs, 10 units refused to take part and 18 hospitals were contacted on 2 occasions but were unable to provide the information due to paucity of time owing to heavy clinical workload. Overall 231 hospitals participated in the audit questionnaire. RESULTS: A total of 30% of the units used oxygen titrated to saturations in accordance with national guidelines. There was no difference between units that had on-site availability of percutaneous coronary intervention and those that did not. Those hospitals where there was a policy for routine oxygen prescription were as unlikely to comply with the guidelines on oxygen use as hospitals where oxygen was not routinely prescribed. CONCLUSION: Only one-third of CCUs in the UK reported adherence to guidelines with regards to oxygen delivery in patients presenting with chest pain. Despite this figure seeming rather low, this is consistent with practice through a range of specialties and guidelines. The evidence base for the oxygen guidance remains insecure. Additional research is required but in the meantime we recommend oxygen is prescribed according to current guidelines.

Indiscriminate coagulation screening of acute medical admissions: national cost ramifications.

BACKGROUND: Routine coagulation screening constitutes poor medical practice and is wasteful of resources. We aimed to determine the extent of inappropriate coagulopathy screening of acute medical admissions in a Scottish general hospital. METHODS: One hundred consecutive medical admissions were prospectively analysed, assessing whether or not a coagulation screen had been conducted on admission and whether or not this was indicated according to current hospital guidelines. Following targeted dissemination of guidelines to appropriate front door medical and nursing staff the audit was repeated. RESULTS: Pre-education, 58% of those for whom coagulation screening was not indicated were being tested. After targeted education, this figure was reduced to 32%. Preeducation, 81% of all patients in whom coagulation screening was indicated were tested. After targeted education, this figure was 86%. CONCLUSION: Indiscriminate coagulation screening is widespread amongst medical admissions to our unit. With simple targeted education, we reduced the rate of inappropriate testing by 26% without reducing the rate of appropriate testing. In a small district general hospital (where the mean local cost for processing a haematology specimen is 8.59 pounds) this translates into a saving of 21,000 pounds per annum. Extrapolated nationwide this represents a cost saving of 1.15 million pounds per annum in Scotland.

Hypogonadism on admission to acute rehabilitation is correlated with lower functional status at admission and discharge.

PRIMARY OBJECTIVE: To investigate the association between hormone levels and functional status during acute TBI rehabilitation. RESEARCH DESIGN: Retrospective cohort study of 43 men with moderate-to-severe TBI admitted to an acute rehabilitation unit during a 1 year period. METHODS AND PROCEDURES: Labs were drawn on admission, including total and free testosterone (T), prolactin, adrenocorticotropin hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (fT4) and insulin-like growth factor (IGF-1). Functional Independence Measure (FIM) scores were obtained at admission and discharge. MAIN OUTCOME AND RESULTS: Associations between admission hormone levels and the main outcomes, admission and discharge FIM scores, were assessed using linear regression. Lower total and free T-levels at admission were associated with lower total FIM scores at admission (p < 0.038) and discharge (p < 0.046). Higher cortisol levels at admission were significantly associated with lower admission (p = 0.012) and discharge (p = 0.036) scores on the cognitive-FIM. Prolactin, TSH, fT4 and IGF-1 were not correlated with functional status. CONCLUSIONS: In men, lower total and free T-levels at admission to acute rehabilitation correlate with lower admission and discharge FIM scores. These data support the need for studies to investigate the impact of physiological testosterone therapy on outcomes during and post-rehabilitation.

Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma.

The objective of this study was to determine the spatial expression of matrix metalloproteinases (MMPs) and their physiologic inhibitors, the tissue inhibitor of MMP (TIMP)-3 and TIMP-4, in ovarian carcinoma compared to normal ovaries. Immunohistochemistry was carried out in this study. Tissue sections prepared from normal ovarian tissues from throughout the menstrual cycle (N = 20) and ovarian carcinomas (N = 45) characterized as stage I (N = 5), stage III/IV (N = 40) were immunostained using polyclonal antibodies to the latent and the active form of MMP-26, TIMP-3, and a monoclonal antibody to TIMP-4. Immunoreactive MMP-26, TIMP-3, and TIMP-4 were detected in all the ovarian cell types in normal and tumor tissues. In normal ovarian tissues, theca externa and luteal cells immunostained with high intensity for MMP-26 and TIMPs while theca/granulosa cell staining intensity increased as lutenization progressed. There was low immunostaining of the ovarian stromal and surface epithelial cells for MMP-26, with moderate staining for TIMPs. In the carcinoma specimens, cancer cells and vascular endothelial cells displayed the highest staining intensity compared to adjacent nontumor areas. The immunostaining intensity of MMP-26 and TIMP-3 increased with stage of tumor with the invading tumor cells displaying the strongest immunostaining. MMP-26, TIMP-3, and TIMP-4 are expressed in normal ovarian as well as ovarian tumors with elevated expression in the invasive tumor cells suggesting a potential role for MMP-26 in normal ovary and ovarian cancer biologic function.

Induction of mosquitocidal activity in mice immunized with Anopheles gambiae midgut cDNA.

Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undue mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.

Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid cytology and absence of INI1 gene mutation.

We report a primary uterine sarcoma with classic histologic, immunohistochemical, and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites, and a right pelvic mass. Malignant cells with rhabdoid morphology were identified by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with transmural infiltration of the myometrium and extensive involvement of uterine serosa and right ovary by tumor. Neoplastic cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of intermediate filaments were observed by electron microscopy. Fluorescence in situ hybridization (FISH) studies with chromosome 22-specific probes showed no loss of the INI1 gene, and no coding sequence mutation was identified.

Charges and lengths of stay for acute and inpatient rehabilitation treatment of traumatic brain injury 1990-1996.

This investigation evaluated yearly trends in charges and lengths of stay for patients with brain injury in acute care and rehabilitation settings over a 7 year period. Data was collected from 800 consecutive patients enrolled in four NIDRR Model Systems Traumatic Brain Injury programmes. Acute care daily charges showed almost routine increases, averaging nearly $550 per year. Conversely, lengths of stay generally showed a downward trend, with annual reductions averaging 2.25 days. Admission lengths of stay averaged 22-29 days between 1990-1994. Admissions averaged less than 20 days beginning in 1995, with the 1996 average of 16 days, nearly half that of the 1993 average. Between 1990-1996, average daily rehabilitation charges increased each year, with the rise averaging $83 or 7%. The rise in daily rehabilitation charges was offset by corresponding decreases in lengths of stay averaging 3.65 days or 8% annually. Increases in daily charges for brain injury rehabilitation care were roughly comparable to those for general medical care prices. However, the rate of change in acute care charges was substantially greater, with annual increases averaging 10% more than national medical care prices. The steady downward trend in lengths of stay raises serious concerns about the future availability of health care services to persons with brain injury.

The expression and action of granulocyte macrophage-colony stimulating factor and its interaction with TGF-beta in endometrial carcinoma.

OBJECTIVE: Previous studies have demonstrated that normal human endometrium expresses granulocyte macrophage-colony stimulating factor (GM-CSF) and GM-CSF receptors. Because GM-CSF is administer to cancer patients following chemotherapy, GM-CSF may directly or through interaction with ovarian steroids and other cytokines alter the behavior of endometrial cancer. The aim of this study was to determine the expression of GM-CSF and receptors in endometrial carcinoma and its direct effect and interaction with transforming growth factor beta (TGF-beta) on Ishikawa cells, a human endometrial carcinoma cell line. METHODS: GM-CSF, GM-CSF receptors, TGF-beta1, and TGF-beta type II receptor expression were evaluated using quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The effect of GM-CSF on DNA synthesis, cell proliferation, expression of GM-CSF, TGF-beta1, and TGF-beta receptor, and their regulation by ovarian steroids was determined by the rate of [(3)H]thymidine incorporation, MTT assay, Q-RT-PCR, and ELISA, respectively. RESULTS: Endometrial carcinomas express significantly higher GM-CSF and GM-CSF alpha and beta receptor mRNA compared with normal postmenopausal endometrium. GM-CSF at various doses had no significant effect on the rate of [(3)H]thymidine incorporation or proliferation of Ishikawa cells, whereas TGF-beta1 inhibited [(3)H]thymidine incorporation. GM-CSF and TGF-beta1 regulate their own expression and the expression of TGF-beta type II receptor, which were both upregulated by 17beta-estradiol and medroxyprogesterone acetate treatment and reversed following cotreatment with their respective receptor antagonists. CONCLUSION: Endometrial carcinoma expresses an elevated level of GM-CSF and GM-CSF receptors. GM-CSF is not a mitogen for the endometrial cancer cell line; however, either alone or through interaction with TGF-beta1, it regulates its own expression and the expression of TGF-beta1 and TGF-beta type II receptor which inhabits endometrial cancer cells. This interaction may represent a regulatory feedback mechanism that could serve to suppress endometrial carcinoma growth.

Predictors for return to work after spinal cord injury: a 3-year multicenter analysis.

OBJECTIVE: To examine the ability of the Motor Index Score (MIS), in combination with demographic variables, to predict return to work during a 3-year period for individuals with spinal cord injury (SCI). METHODS: Prospectively collected data, between 1986 and 1995, submitted to the National Spinal Cord Injury Statistical Center were analyzed to determine the prediction of return to work utilizing variables of education, ethnicity, age, marital status, gender, and MIS. Individuals, aged 18 to 65 yrs, employed at the time of their injury, were evaluated at discharge from rehabilitation and at 1 (YR1), 2 (YR2), and 3 (YR3) years postinjury (sample sizes of 1,857, 1,486, and 1,177, respectively). RESULTS: The most important predictors of return to work were education, MIS, ethnicity, and age at onset of SCI. These variables resulted in a high rate of accuracy for predicting across all 3 yrs (YR1, 81%; YR2, 82%; YR3, 77%). CONCLUSIONS: The ability to predict return to work after SCI was shown utilizing MIS and demographic variables, with nearly 80% accuracy. This suggests that return to work after SCI is a dynamic process, with the level of importance of each variable changing with time postinjury.