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Balancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. TCR-sequencing of the primary tumor, a hepatic metastasis, duodenal biopsy and peripheral blood mononuclear cells, identified the identical T cell clone in all four tissues. This case provides preliminary evidence for cross-reactivity as a mechanism for the association between effect and toxicity of ICIs. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this review were to calculate the diagnostic accuracy statistics of risk scales following self-harm and consider which might be the most useful scales in clinical practice. Design: Systematic review. Methods: We based our search terms on those used in the systematic reviews carried out for the National Institute for Health and Care Excellence self-harm guidelines (2012) and evidence update (2013), and updated the searches through to February 2015 (CINAHL, EMBASE, MEDLINE, and PsychINFO). Methodological quality was assessed and three reviewers extracted data independently. We limited our analysis to cohort studies in adults using the outcome of repeat self-harm or attempted suicide. We calculated diagnostic accuracy statistics including measures of global accuracy. Statistical pooling was not possible due to heterogeneity. Results: The eight papers included in the final analysis varied widely according to methodological quality and the content of scales employed. Overall, sensitivity of scales ranged from 6% (95% CI 5% to 6%) to 97% (CI 95% 94% to 98%). The positive predictive value (PPV) ranged from 5% (95% CI 3% to 9%) to 84% (95% CI 80% to 87%). The diagnostic OR ranged from 1.01 (95% CI 0.434 to 2.5) to 16.3 (95%CI 12.5 to 21.4). Scales with high sensitivity tended to have low PPVs. Conclusions: It is difficult to be certain which, if any, are the most useful scales for self-harm risk assessment. No scales perform sufficiently well so as to be recommended for routine clinical use. Further robust prospective studies are warranted to evaluate risk scales following an episode of self-harm. Diagnostic accuracy statistics should be considered in relation to the specific service needs, and scales should only be used as an adjunct to assessment. [ABSTRACT FROM AUTHOR]

Objective: Safe midwifery staffing levels on delivery suites is a priority area for any maternity service. Escalation policies are tools that provide an operational response to emergency pressures. The aim of this study was to assess the feasibility of using a scoring system to contemporaneously assess the required staffing level based on demand and use this to determine delivery suite escalation level and utilise the information generated regarding clinical activity (Demand) and staffing levels (Capacity) to generate unit-specific calculation for the actual number of midwifery staff required. Setting: A maternity unit of a university-affiliated tertiary referral hospital. Design: Over a 12-month period, specifically designed scoring sheets were completed by delivery suite shift co-ordinators four times a day (04:00, 10:00, 16:00 and 22:00). Based on the dependency score (Demand) and the number of midwifery staff available (Capacity), an escalation level was determined for each shift. The 80th centile of the demand was used to determine optimal capacity. Results: A total of 1160 scoring sheets were completed. Average staff number throughout the year on any shift was 7 (range 3-11). Average dependency score was 7 (range 1-14). The 80th centile for demand was calculated to be 11. Conclusions: This study stresses the importance and usefulness of a simple tool that can be used to determine the level of escalation on delivery suite based on an objective scoring system and can also be used to determine the appropriate staffing on delivery suite. [ABSTRACT FROM AUTHOR]

Objective: To investigate the extent to which risk scales were used for the assessment of self-harm by emergency department clinicians and mental health staff, and to examine the association between the use of a risk scale and measures of service quality and repeat self-harm within 6 months. Design: Observational study. Setting: A stratified random sample of 32 hospitals in England. Participants: 6442 individuals presenting with self-harm to 32 hospital services during a 3-month period between 2010 and 2011. Outcomes: 21-item measure of service quality, repeat self-harm within 6 months. Results: A variety of different risk assessment tools were in use. Unvalidated locally developed proformas were the most commonly used instruments (reported in n=22 (68.8%) mental health services). Risk assessment scales were used in one-third of services, with the SAD PERSONS being the single most commonly used scale. There were no differences in service quality score between hospitals which did and did not use scales as a component of risk assessment (median service quality score (IQR): 14.5 (12.8, 16.4) vs 14.5 (11.4, 16.0), U=121.0, p=0.90), but hospitals which used scales had a lower median rate of repeat self-harm within 6 months (median repeat rate (IQR): 18.5% vs 22.7%, p=0.008, IRR (95% CI) 1.18 (1.00 to 1.37). When adjusted for differences in casemix, this association was attenuated (IRR=1.13, 95% CI (0.98 to 1.3)). Conclusions: There is little consensus over the best instruments for risk assessment following self-harm. Further research to evaluate the impact of scales following an episode of self-harm is warranted using prospective designs. Until then, it is likely that the indiscriminant use of risk scales in clinical services will continue. [ABSTRACT FROM AUTHOR]

Objectives: To describe the characteristics and management of individuals attending hospital with self-harm and assess changes in management and service quality since an earlier study in 2001, a period in which national guidance has been available. Design: Observational study. Setting: A stratified random sample of 32 hospitals in England, UK. Participants: 6442 individuals presenting with 7689 episodes of self-harm during a 3-month audit period between 2010 and 2011. Outcome: Self-harm episodes, key aspects of individual management relating to psychosocial assessment and follow-up, and a 21-item measure of service quality. Results: Overall, 56% (3583/6442) of individuals were women and 51% (3274/6442) were aged under 35 years. Hospitals varied markedly in their management. The proportion of episodes that received a psychosocial assessment by a mental health professional ranged from 22% to 88% (median 58%, IQR 48-70%); the proportion of episodes resulting in admission to general hospitals varied from 22% to 85% (median 54%, IQR 41-63%); a referral for specialist mental health follow-up was made in 11-64% of episodes (median 28%, IQR 22-38%); a referral to non-statutory services was made in 4-62% of episodes (median 15%, IQR 8-23%); 0-21% of episodes resulted in psychiatric admission (median 7%, QR 4-12%). The specialist assessment rate varied by method of harm; the median rate for self-cutting was 45% (IQR 28-63%) vs 58% (IQR 48-73%) for self-poisoning. Compared with the 2001 study, there was little difference in the proportion of episodes receiving specialist assessment; there was a significant increase in general hospital admission but a decrease in referrals for specialist mental health follow-up. However, scores on the service quality scale had increased from a median of 11.5-14.5 (a 26% increase). Conclusions: Services for the hospital management of self-harm remain variable despite national guidelines and policy initiatives. We found no evidence for increasing levels of assessment over time but markers of service quality may have improved. This paper forms part of the study 'Variations in self-harm service delivery: an observational study examining outcomes and temporal trends'. The National Institute for Health Research Clinical Research Network (NIHR CRN) Portfolio database registration number: HOMASH 2 (7333). The NIHR Coordinated System for gaining NHS Permission (CSP) registration number: 23226. [ABSTRACT FROM AUTHOR]

Background and Aims: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (-572G>C and -174G>C) with intracranial aneurysms was tested.Methods: IL-6 genotypes were determined in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK controls.Results: For both polymorphisms, the distribution of the genotypes and estimated allele frequency were different between the control group and the aneurysm group. For -572G>C, a higher frequency of the C allele (p = 0.001) and more people homozygous for the C allele were found among those with aneurysms than among the controls (4.4% v 0.3%, p = 0.001). For -174G>C, more people homozygous for the C allele were found among the controls than among those with aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an increased risk of aneurysms, with the relative risk compared with the common haplotype being 1.89 and that for the -572G/174C haplotype being 0.58 (p<0.0005).Conclusion: This is the first study to show that IL-6 promoter polymorphisms are associated with intracranial aneurysmal disease. Whether this association is with the development, progression or rupture of such aneurysms, or represents survivor bias, is unclear. [ABSTRACT FROM AUTHOR]

Aims: To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9L and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined definite familial hypercholesterolaemia in UK. Patients and methods: 409 patients with familial hypercholesterolaemia patients (158 with CHD) were studied. The LDLR was partially screened by single-strand conformational polymorphism (SSCP) (exons 3, 4, 6-10 and 14) and by using a commercial kit for gross deletions or rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. Results: Mutations were detected in 253 (61.9%) patients: 236 (57.7%) carried LDLR, 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1 .84 (95% CI 1.10 to 3.06), for APOB 3.40 (0.71 to 16.36), and for PCSK9 19.96 (1.88 to 211.5; p=0.001 overall). The high risk in patients carrying LDLR and PCSK9 p.Y374 was partly explained by their higher pretreatment cholesterol levels (LDLR, PCSK9 and no mutation, 10.29 (1.85), 13.12 and 9.85 (1.90) mmol/l, respectively, p=0.001). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than in patients with no identified mutation (LDL-C, 6.77 (1.82) mmol/l v 4.19 (1.26) mmol/l, p=0.001, HDL-C 1.09 (0.27) mmol/l v 1.36 (0.36) mmol/l, p=0.03). Conclusions: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of patients with familial hypercholesterolaemia. Mutations in PCSK9 appear uncommon in patients with familial hypercholesterolaemia in UK. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether case fatality rates in South Asian (Bangladeshi, Indian and Pakistani) patients with acute myocardial infarction have shown similar declines to those reported for white patients during the past 15 years. Design: Cross-sectional, observational study. Setting: Coronary care unit in east London. Patients: 2640 patients-29% South Asian-admitted with acute myocardial infarction between January 1988 and December 2002. Main outcome measures: Differences over time in rates of in-hospital death, ventricular fibrillation and left ventricular failure. Results: The proportion of South Asians increased from 22% in 1988-92 to 37% in 1998-2002. Indices of infarct severity were similar in South Asian and white patients, with declining frequencies of ST elevation infarction (88.2% to 77.5%, p < 0.0001), Q wave development (78.1% to 56.9%, p <0.0001) and mean (interquartile range) peak serum creatine kinase concentrations (1250 (567-2078) to 1007 (538-1758) IU/l, p < 0.0001) between 1988-92 and 1998-2002. Rates of in-hospital death (13.0% to 9.4%, p < 0.01), ventricular fibrillation (9.2% to 6.0%, p < 0.001) and left ventricular failure (33.2% to 26.5%, p < 0.0001) all declined; these changes did not interact significantly with ethnicity. Odds ratios for the effect of time on risk of death increased from 0.81 (95% CI 0.70 to 0.93) to 1.02 (95% CI 0.87 to 1.21) after adjustment for ethnicity and indices of infarct severity (ST elevation, peak creatine kinase, Q wave development and treatment with a thrombolytic). Conclusions: In the past 15 years, death from acute myocardial infarction among South Asians has declined at a rate similar to that seen in white patients. This is largely caused by reductions in indices of infarct severity. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the impact the National Service Framework (NSF) for coronary heart disease has had on emergency treatment and outcomes in patients presenting with acute coronary syndromes. DESIGN: Retrospective cohort study. SETTING: Coronary care units of two district general hospitals. RESULTS: Data from 3371 patients were recorded, 1993 patients in the 27 months before the introduction of the NSF and 1378 patients in the 24 months afterwards. After the introduction of the NSF in-hospital mortality was significantly reduced (95 patients (4.8%) v 43 (3.2%), p = 0.02). This was associated with a reduction in the development of Q wave myocardial infarction (40.6% v 33.3%, p < 0.0001) and in the incidence of left ventricular failure (15.9% v 12.3%, p = 0.003). The proportion of patients receiving thrombolysis increased (69.4% v 84.7%, p < 0.0001) with a decrease in the time taken to receive it (proportion thrombolysed within 20 minutes 12.1% v 26.6%, p < 0.0001). The prescription of beta blockers (51.9% v 65.8%, p < 0.0001), angiotensin converting enzyme inhibitors (37% v 66.4%, p < 0.0001), and statins (55.2% v 72.7%, p < 0.0001) improved and the proportion of patients referred for invasive investigation increased (18.3% v 27.0%, p < 0.0001). Trend analysis showed that improvements in mortality and thrombolysis were directly associated with publication of the NSF, whereas the improvements seen in prescription of beta blockers and statins were the continuation of pre-existing trends. CONCLUSIONS: In the two years that followed publication of the NSF the initial treatment and outcome of patients presenting with acute coronary syndromes improved. Some of the improvements can be attributed to the NSF but others are continuations of pre-existing trends. [ABSTRACT FROM AUTHOR]

Purpose: To compare base-in prism reading glasses with placebo reading glasses for the treatment of symptomatic convergence insufficiency (CI) in children aged 9 to <18 years. Methods: In a randomised clinical trial, 72 children aged 9 to <18 years with symptomatic CI were assigned to either base-in prism glasses or placebo reading glasses. Symptom level, measured with a quantitative symptom questionnaire (CI Symptom Survey-V15), was the primary outcome measure. Near point of convergence and positive fusional vergence at near were secondary outcomes. Results: The mean (SD) CI Symptom Survey score decreased (that is, less symptomatic) in both groups (base-in prism glasses from 31.6 (10.4) to 16.5 (9.2); placebo glasses from 28.4 (8.8) to 17.5 (12.3)). The change in the CI Symptom Survey scores (p = 0.33), near point of convergence (p = 0.91), and positive fusional vergence (p = 0.59) were not significantly different between the two groups after 6 weeks of wearing glasses. Conclusions: Base-in prism reading glasses were found to be no more effective in alleviating symptoms, improving the near point of convergence, or improving positive fusional vergence at near than placebo reading glasses for the treatment of children aged 9 to <18 years with symptomatic CI. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes.Methods: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed.Results: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09).Conclusion: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incremental value of clinical data, troponin T, ST segment monitoring, and heart rate variability for predicting outcome in patients with non-ST elevation acute coronary syndromes.Methods: Prospective cohort study of 304 consecutive patients. Baseline clinical and electrocardiographic data were recorded, serial blood samples were obtained for troponin T assay, and 48 hour Holter monitoring was performed for ST segment and heart rate variability analysis. End points were cardiac death and non-fatal myocardial infarction during 12 months' follow up.Results: After 12 months, 7 patients had died and 21 had had non-fatal myocardial infarction. The risk of an event was increased by troponin T > 0.1 microg/l, T wave inversion on the presenting ECG, Holter ST shift, and a decrease in the standard deviation of 5 minute mean RR intervals. Positive predictive values of individual multivariate risk were low; however, analysis of all multivariate risk markers permitted calculation of a cumulative risk score, which increased the positive predictive value to 46.9% while retaining a negative predictive value of 96.9%.Conclusion: A cumulative approach to risk stratification in non-ST elevation coronary syndromes successfully identifies a group in whom the risk of cardiac death or non-fatal myocardial infarction approaches 50%. [ABSTRACT FROM AUTHOR]

Background: Shortening prehospital delay has been identified as an important means of improving responses to reperfusion treatment. If this increases the risk profile of the population delivered to hospital, it may paradoxically cause a deterioration in hospital mortality. Objective: To examine the interaction between arrival time (time from onset of chest pain to arrival at hospital) and thrombolytic treatment in determining the early outcome of acute myocardial infarction. Methods: Prospective cohort study of 1723 patients with acute myocardial infarction who were potentially eligible for thrombolytic treatment (ST elevation on ECG; arrival time ≤ 12 hours). Results: All patients were eligible for thrombolysis but only 1098 (80%) received it. Patients who did not receive thrombolytic treatment were older (66 (58-73) v 61 (53-70) years, p < 0.001), more commonly female (32.1% v 24.8%, p < 0.01), and had higher frequencies of previous infarction (28.6% v 15.6%, p < 0.001) and left ventricular failure (37.5% v 26.9%, p < 0.01) than patients who received thrombolytic treatment. For the group as a whole, 30 day mortality was 11.7% and was unaffected by arrival time, but in patients who did not receive thrombolysis an arrival time of ≤ 6 hours was associated with significantly higher 30 day mortality than an arrival time of 6-12 hours (24.3% v 2.6%, p = 0.002). Conversely, in patients who did receive thrombolysis an arrival time of ≤ 6 hours was associated with a lower 30 day mortality than an arrival time of 6-12 hours (8.5% v 14.5%, p < 0.02). Conclusions: Shortening prehospital delay in acute myocardial infarction will tend to increase the risk profile of patients presenting to emergency departments. The data presented here indicate that this may increase hospital mortality if underutilisation of thrombolytic treatment among high risk groups is not diminished. [ABSTRACT FROM AUTHOR]

The article presents a prospective study which investigates the relationship between subsequent fatal ischaemic heart disease (IHD) and psychological characteristics events. The study includes 1408 white men aged 40-64 years without a history of myocardial infarction to finish a Crown-Crisp experiential index form (CCEI). Results show that the associations were independent of social class, age, and known cardiovascular risk factors.

Suppression scotomas and retinal projection (retinal correspondence) were measured in six intermittent exotropes during deviation. Measurements used red-green anaglyph stimuli presented on a black background which could be varied from 3.4 minutes of arc to 3 degrees 24'. Results showed non-suppression of all points between the fovea and the diplopia point. Harmonious anomalous retinal correspondence was usually observed. Two subjects had spontaneous changes from anomalous retinal correspondence to normal retinal correspondence without a concurrent change in ocular position. Conventional testing resulted in more variable results in regard to retinal correspondence and suppression, suggesting that non-suppression and anomalous retinal correspondence occur when black backgrounds are used for testing. [ABSTRACT FROM PUBLISHER]

Objective infrared recording devices were used to measure simultaneously and continuously both accommodation and accommodative vergence to near stimuli in 4 subjects with intermittent exotropia of the divergence-excess type (2 simulated and 2 true). In addition standard clinically determined stimulus accommodative convergence to accommodation (AC/A) ratios were measured. Results showed the mean group response AC/C ratio to be 5.9/1 (range 4.5-8.0/1) with no differences between true and simulated divergence-excess. Similar AC/A ratios were found after 45 minutes of monocular occlusion. Our results clearly demonstrate relatively normal response AC/A ratios in these subjects. Thus, contrary to what is believed by many clinicians, the reduced ocular deviation at near compared with distance vision cannot be attributed primarily to an abnormally high AC/A ratio. We believe than fusional convergence after-effects and/or proximal convergence effects contribute to inflate the clinically determined stimulus AC/A ratios. [ABSTRACT FROM PUBLISHER]

Studies of reaction time in Parkinson's disease (PD) have suggested a selective deficit in simple reaction time (SRT), compared with choice reaction time (CRT). This finding has been interpreted as a deficit in motor preprogramming but could involve other factors, such as attentional focussing and stimulus predictability. Moreover, not all studies show the same selective deficit, possibly because of differences in patient selection and treatment effects. The neurochemical basis of RT deficits in PD remains unclear. Accordingly, the contribution of cognitive factors to impaired RT was assessed in a large group of PD patients, including early untreated cases, and performance was examined in relation to clinical variables and the effect of treatment in longitudinal study. Motor output was constant in both SRT and CRT tasks. In the SRT task, all stimuli required a response; in the CRT task, subjects were required to respond to only one of the two possible stimuli. Attentional focussing on SRT was examined by variation of the interval between cue and stimulus; effects of stimulus uncertainty were evaluated from a comparison of SRT and CRT; temporal predictability of the stimulus was examined from a comparison of conditions in which the interval between warning signal and imperative stimulus was constant or variable. The PD patients showed similar deficits in SRT and CRT, but normal effects of cue-stimulus interval and temporal predictability. Reaction time correlated with measures of global cognitive capacity and frontal-lobe function, as well as motor disability. Treatment had no effect on SRT or CRT, despite clinical benefit. These findings indicate that RT deficits in PD are not due to impaired attentional focussing or stimulus predictability but are compatible with a deficit in higher-order processes concerned with the orientation of both cognitive and motor responses to a stimulus. These processes are not substantially dopamine-dependent but may be served by non-dopaminergic neurotransmission. [ABSTRACT FROM AUTHOR]

Paradigms of isometric force control allow study of the generation and release of movement in the absence of complications due to disordered visuomotor coordination. The onset and release of isometric force in Parkinson's disease (PD) was studied, using computerised determinants of latency of response and rate of force generation and release. Components of isometric force control were related to measures of cognitive, affective and clinical motor disability. The effects of treatment were determined by longitudinal study of de novo patients. Patients with PD showed impairment in latency and rate of force change for movement release as well as onset. Rate of force change correlated with depression, clinical motor disability and memory quotient but latency showed no correlation with any of these measures. Treatment improved rate of force release, in concert with clinical motor disability, but not latency. These results suggest dissociations between latency and rate of force change that may be linked to different neurochemical deficits. Further, they demonstrate akinetic deficits in force release that argue against the "neural energy hypothesis" of akinesia. [ABSTRACT FROM AUTHOR]

A survey in the London Borough of Croydon was conducted among an entire school cohort, aged about 9 years, to describe the current morbidity from wheezing illness, its relation to social and family factors, and its effects on social and educational development. A postal screening questionnaire was sent to 5100 parents, and 11.1% of the children were reported to have had wheezing illness over the previous 12 months. A sample of 284 parents were subsequently interviewed at home about their child's illness. School absence over the past year caused by wheezing illness was reported by 58%; and in 12% of children this amounted to more than 30 school days. School absence was strongly associated with all other indicators of morbidity-- short and long term. The proportion described as having "asthma' rose from 22% in those with no absence, to 50% in those with more than 30 days absence. Compared with 92 randomly selected controls with no history of wheezing, wheezy children had more atopic conditions, recurrent headaches, and abdominal pains. School absence was associated with parental separation, non-manual occupation of the mother, more than three children in the household, poor maternal mental health, lack of access to a car, and renting of accommodation. The child's illness had substantial effects on the activities of the mother and the rest of the family, but not on the child's social and recreational activities. Children with over 6 weeks' school absence scored appreciably worse on a teacher's assessment of their social, psychological, and educational adjustment. [ABSTRACT FROM AUTHOR]

Objective: To define the clinical value of the signal averaged P wave (SAPW) and to compare it with the standard electrocardiogram (ECG), echocardiogram, and clinical assessment for the prediction of atrial fibrillation after coronary bypass grafting (CABG).Design: Prospective validation cohort study.Setting: Regional cardiothoracic centre.Patients: 201 unselected patients undergoing first elective CABG were recruited over six months. Patients requiring concomitant valve surgery were excluded.Main Outcome Measures: Age, sex, cardiothoracic ratio, and cardioactive drugs were noted. P wave specific SAPW recordings, ECG, and M mode echocardiograms from which left atrial diameter was measured were performed within 24 hours of surgery. Filtered P wave duration (SAPWD), spatial velocity, and energy were calculated from the SAPW. From the ECG, lead II P wave duration, P terminal force in lead V1, total P wave duration, and isoelectric interval were measured. Patients had Holter monitoring for 48 hours postoperatively and daily ECGs until discharge.Results: Two patients died (1%) and 10 were unsuitable for analysis (5%). Of the remaining 189, 51 (27%) had atrial fibrillation (AF) lasting > 1 hour at a mean of 2 (0.5 to 7) days after CABG. Of the variables examined, only SAPWD (AF group 148 (SD 12), v 142 (14) ms, P = 0.008) and male sex (AF group 96%, v 78%, P < 0.01) were significantly different. A prospectively defined SAPWD of > 141 ms predicted atrial fibrillation with positive and negative predictive accuracies of 34% and 83%. Logistic regression analysis identified both male sex and SAPWD as significant independent predictors of postoperative atrial fibrillation.Conclusions: Signal averaged P wave duration was a better predictor of atrial fibrillation after coronary bypass grafting than standard electrocardiographic or echocardiographic criteria. The predictive value of this test is such that it is likely to be useful in the design of prospective trials of prophylactic antiarrhythmic treatment but is of limited use using current techniques in the clinical management of individual patients. [ABSTRACT FROM AUTHOR]

Objective: To assess the reproducibility of time and frequency domain variables derived from the signal averaged P wave.Design: Longitudinal within patient study.Setting: Regional cardiothoracic centre.Patients: 20 patients (10 with documented paroxysmal atrial fibrillation and 10 normal controls) were studied on three occasions to assess the reproducibility of repeated signal averaged P wave recordings. Digital P wave recordings were made on a further 10 patients on a single occasion and the recordings signal averaged twice in order to assess the reproducibility of the averaging system itself in the absence of biological variation.Main Outcome Measures: P wave duration, spatial velocity, and energies contained in frequency bands from 20, 30, and 60-150 Hz of the P wave spectrum were measured after P wave specific signal averaging. Coefficients of reproducibility were calculated for paired signal averaged P waves derived by signal averaging the same digital recordings on two separate occasions, for recordings performed in the same patients immediately after each other ("back to back") and those performed one week apart.Results: System reproducibility when the same digital P wave recordings were signal averaged on two separate occasions was high (< 11% for all variables). For P wave duration the coefficient of reproducibility was 11.4% for back to back recordings and 13.1% for those one week apart. The reproducibility of spatial velocity and P wave energy was low. Variation in P wave morphology was noted when successive P waves from the same subject were examined. If recordings with the same P wave morphology were analysed the reproducibility of spatial velocity and P wave energy improved but remained significantly poorer than that for P wave duration.Conclusions: P wave duration is reproducible within subjects in the short and medium term. Frequency domain and spatial velocity analysis are poorly reproducible, due more to spontaneous variation in P wave morphology than to instability of the signal averaging process. This may limit the utility of signal averaged P wave variables other than duration for the prediction of atrial arrhythmia. [ABSTRACT FROM AUTHOR]

We have investigated factors affecting the probability that a woman with breast cancer participating in a mammographic screening programme will be diagnosed by the screen. Data from a large American case-control study, with subjects drawn from women participating in an annual screening programme, were used. During the screening programme, 409 cases were identified, the mode of diagnosis being screen detection for 331 and interval detection for 78. No significant relationships were found between mode of diagnosis and age, age at menarche, oral contraceptive use, age at first live birth, age at menopause or history of maternal breast cancer. There was a non-significant trend for particular mammographic patterns to be associated with interval detection. However relative risk of breast cancer and probability of interval detection were observed to increase about the time of the menopause. These results suggest that the 3 yearly mammography programme being introduced in the UK might be improved if an extra examination was included around the time of the menopause. [ABSTRACT FROM PUBLISHER]

A survey was carried out to investigate the medical care of asthma and wheezing illness in a school population. Children with current wheezing illness were identified by a screening questionnaire to the parents of 5100 children in one school cohort from all schools in an outer London borough. Of the 89% who responded, 11.1% reported wheezing within the past 12 months. Parents of a sample of 284 wheezy children aged about 9 were interviewed at home about their child's illness and the related use of drugs and services. There was evidence of substantial underuse of services and this was not associated with social, family, or general practice factors. Considerable proportions of children were not having drug treatment, were receiving only non-antiasthmatic drugs, or were using antiasthmatic drugs incorrectly. The most important social and family factor associated with undertreatment was poor maternal mental health, and this factor appeared to explain the observed association of manual social class with undertreatment. Only about half of the most severe group were labelled as having "asthma," and those with this label were more likely to be receiving treatment and using outpatient services. The results show that the potential of modern treatment to prevent disability due to wheezing illness is not being realised despite the existence of a free and accessible health service. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To investigate the effects of low dose sotalol on the signal averaged surface P wave in patients with paroxysmal atrial fibrillation. DESIGN--A longitudinal within patient crossover study. SETTING--Cardiac departments of a regional cardiothoracic centre and a district general hospital. PATIENTS--Sixteen patients with documented paroxysmal atrial fibrillation. The median (range) age of the patients was 65.5 (36-70) years; 11 were men. MAIN OUTCOME MEASURES--Analysis of the signal averaged P wave recorded from patients not receiving antiarrhythmic medication and after 4-6 weeks' treatment with sotalol. P wave limits were defined automatically by a computer algorithm. Filtered P wave duration and energies contained in frequency bands from 20, 30, 40, 60, and 80 to 150 Hz of the P wave spectrum expressed as absolute values (P20, P30, etc) and as ratios of high to low frequency energy (PR20, PR30, etc) were measured. RESULTS--No difference in P wave duration was observed between the groups studied (mean (SEM) 149 (4) without medication and 152 (3) ms with sotalol). Significant decreases in high frequency P wave energy (for example P60: 4.3 (0.4) v 3.3 (0.3) microV2.s, P = 0.003) and energy ratio (PR60: 5.6 (0.5) v 4.7 (0.6), P = 0.03) were observed during sotalol treatment. These changes were independent of heart rate. CONCLUSIONS--Treatment with low dose sotalol reduces high frequency P wave energy but does not change P wave duration. These results are consistent with the class III effect of the drug and suggest that signal averaging of the surface P wave may be a useful non-invasive measure of drug induced changes in atrial electrophysiology. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To identify features associated with success or failure of aspiration of pericardial effusion. METHOD--A retrospective analysis of 36 drainage procedures in 30 patients with pericardial effusion was performed using patient records and echocardiograms. RESULTS--Unsuccessful aspiration was associated with pericardial loculation but not with the seniority of the operator or the size and position of the effusion. Pericardiocentesis relieved symptoms of breathlessness in 21 of 26 patients who had a pericardial effusion suspected of causing dyspnoea. These 21 patients had few clinical or echocardiographic signs of classic tamponade. CONCLUSION--The paucity of abnormal physical or echocardiographic signs of tamponade in breathless patients with pericardial effusion does not exclude symptomatic benefit being derived from pericardiocentesis. Pericardial aspiration is safe in appropriate hands, although aspiration of loculated effusions may not be as successful as aspiration of non-loculated effusions. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To assess the incidence and complications of permanent pacing in patients who undergo tricuspid valve replacement. DESIGN--A retrospective study of records of patients who had a tricuspid valve replacement between 1978 and 1993 at the Middlesex hospital. RESULTS--45 patients with tricuspid valve replacements were followed up for a total of 104 patient years. Ten patients (22%) required permanent pacing, five with epicardial leads and five with endocardial. Endocardial leads had significantly lower initial implantation thresholds and were associated with fewer complications. CONCLUSION--Patients undergoing tricuspid valve replacement frequently require permanent pacing. Endocardial or epicardial lead insertion should be considered at the time of tricuspid valve replacement. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To assess the effect of physical activity on plasma fibrinogen and factor VII activity and thus on the risk of ischaemic heart disease. DESIGN--Cross sectional survey. SETTING--Ten group practices in the Medical Research Council's General Practice Research Framework. PATIENTS--3967 men aged 45-69 attending screening clinics for the thrombosis prevention trial. METHODS--Structured interview to elicit the intensity and frequency of physical exercise during past month. Measurement of fibrinogen, factor VII activity, cholesterol concentration, blood pressure, and other indices of ischaemic heart disease risk. RESULTS--Strenuous exercise was associated with significantly lower fibrinogen concentrations than mild exercise, implying a difference of about 15% in the risk of ischaemic heart disease. Strenuous exercise was also associated with lower cholesterol concentrations. More frequent strenuous exercise was associated with lower factor VII activity. CONCLUSIONS--With the recognition of plasma fibrinogen as a strong index of ischaemic heart disease risk the results of this and other studies suggest a pathway through which the protective effect of strenuous exercise may partly be mediated and they provide doctors and patients with a valuable incentive towards prevention, particularly in those whose risk of ischaemic heart disease is substantially due to raised fibrinogen concentrations. [ABSTRACT FROM PUBLISHER]

This report describes two patients with a distinctive type of dicentric autosomal chromosome formed by breakage and union between homologous chromosomes. These stable chromosomes possess two C bands, implying the presence of two centromeric regions. The first child, evaluated for dysmorphic features was shown to have an abnormal chromosome 16, designated as 46, XX, -16, + dic (16) (pter leads to cen leads to q22::p11 leads to qter). The second case is a child with the typical features of trisomy 18 whose karyotype is designated as 46, XX, -18, + dic (18) (qter leads to p11.1 :: p11.3 leads to cen leads to qter). The stability of these chromosomes is presumably in result of centromere suppression and associated premature centromere division of the suppressed centromere. The possible mechanism of formation of these homodicentric chromosomes is presented, and a comparison is made between them and three patients with dicentric X chromosomes. [ABSTRACT FROM PUBLISHER]

Body composition was measured in 24 patients who had previously undergone proctocolectomy and ileostomy. One group (control group) had undergone resection of only small amounts of terminal ileum (median 4 cm), the other group of patients (resected group) had undergone resection of greater lengths of small bowel (median 54 cm). These values of body composition were then compared with predicted values in normal subjects. Proctocolectomy and ileostomy without ileal resection did not significantly affect body weight, or the body contents of fat or water, but led to a reduction in total body nitrogen and total body potassium, suggesting a reduction in fat free mass. A modest resection of the terminal ileum undertaken during the course of proctocolectomy decreased body weight largely because of a reduction in body fat. None of the ileostomy patients was found to be dehydrated. [ABSTRACT FROM PUBLISHER]

Mutagenicity has been measured in the gastric juice of 228 patients using the Ames bacteriological test system; while mutagenicity in control and duodenal ulcer patients did not differ from saline controls, mutagenicity was significantly increased compared with controls in patients suffering gastric ulcer (p less than 0.002), carcinoma (p less than 0.002), and in patients after gastric resection (p less than 0.01). A transient rise in mutagenicity was seen following H2 antagonist ingestion (p less than 0.002). Increased levels of mutagenicity were found to correlate closely with gastric juice pH and bacterial count. Histidine concentrations in gastric juice did not explain the mutagenicity results. [ABSTRACT FROM PUBLISHER]

The article presents a summary of 12 reviews from the Cochrane Database of Systematic Reviews produced by the Renal Group. It has been observed that in the article "Non-Steroidal Anti-Inflammatory Drugs Versus Opioids for Acute Renal Colic," non-steroidal anti-inflammatory drugs (NSAID) can be used in the treatment of renal colic. The reviewers agree with the article "Long-Term Antibiotics for Preventing Recurrent Urinary Tract Infection in Children," which presents evidence suggesting that antibiotics prevents some infections.

The article examines Cochrane Reviews applicable to emergency services (SOCRATES) discovered in the assessment of the output of the Cochrane Heart Group. The goal of the review was to find out whether active compression-decompression cardiopulmonary resuscitation (CPR) using a handheld suction device improved mortality compared with using standard manual CPR in adults with cardiac arrest. Results of the review showed that warfarin is effective in preventing stroke among patients with atrial fibrillation while aspirin is inconclusive.

Guillain-Barré syndrome is considered to be an immune mediated disorder but the relative role of T cells and antibodies in its pathogenesis is unclear. As gut infection with Campylobacter jejuni is the most common antecedent infection it is possible that gut derived T lymphocytes might play a part in the development of the syndrome. The T cell receptor phenotype (TCR) of a nerve gamma delta T cell line obtained from a sural nerve biopsy taken from a patient with a demyelinating form of GBS was determined using polymerase chain reaction (PCR) and flow cytometry (FACS). This TCR was compared with the phenotype preferentially expressed in the peripheral blood of the same patient. The T cell nerve line was found to express V gamma 8/delta 1 which represents an unusual T cell subset normally found on lymphocytes resident in epithelial tissue such as the gut. The peripheral blood gamma delta T lymphocytes from the patient were of the V gamma 9/delta 2 subset, which is the phenotype predominantly expressed in the peripheral blood of healthy subjects. In conclusion, the presence of this unusual population of V gamma 8/delta 1(+) lymphocytes in nerve would be consistent with a pathogenetic role for gut associated lymphocytes in the pathogenesis of Guillain-Barré syndrome associated with C jejuni. [ABSTRACT FROM AUTHOR]

Head up tilt is an established test for assessing patients with vasovagal syncope. Prolonged asystole during the test has previously been reported in patients suffering from the malignant form of this syndrome. Little is known about the prognostic significance of this response and there is no consensus about the optimum treatment. Four such patients are reported who were treated pharmacologically. During follow up they remained free from major events and their symptoms were well controlled. Conservative management is the initial method of choice and only if this fails should implantation of a dual chamber permanent pacemaker be considered. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate an association previously reported in a retrospective study between the A phenotype and social classes I and II. The study was a prospective survey using a cohort of blood donors. Participants were donors at a regional blood bank in southern Ireland servicing a population of approximately 380,000. Of 2442 donors considered for inclusion in the study, 21 refused to participate, 33 provided insufficient information, and 184 were excluded because they were not wholly of Irish extraction, leaving a total of 2204 subjects, 64% of whom were male. Occupation, age and birth place were obtained from a short questionnaire given to all potential donors during the study period. Social class was defined according to the United Kingdom Registrar General's criteria. No association between the ABO phenotype and social class could be found, either on the whole sample, or on currently employed persons, or on separate analysis of the sexes. The balance of current evidence is against a variation in ABO distribution by social class designation. [ABSTRACT FROM AUTHOR]

A false aneurysm of the pulmonary artery developed in a 59 year old woman as a complication of right-sided cardiac catheterisation. This rare, life-threatening condition was successfully treated with coil embolisation of the feeding artery. Cardiologists and intensive care doctors should be aware of the possibility of the formation of false aneurysms of the pulmonary artery after Swan-Ganz and other right heart catheterisation. Appropriate therapy could be life-saving. [ABSTRACT FROM PUBLISHER]

Serum troponin estimation is widely used in the diagnosis and management of coronary syndromes, but it is possible to be misled by a positive result unless it is put carefully into clinical context. The serum troponin can be positive in pulmonary embolus and carries prognostic significance. A case report is presented and a review of the relevant literature. [ABSTRACT FROM AUTHOR]