Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Arterial pulse pressure and postoperative morbidity in high-risk surgical patients.

BACKGROUND: Systemic arterial pulse pressure (systolic minus diastolic pressure) ≤53 mm Hg in patients with cardiac failure is correlated with reduced stroke volume and is independently associated with accelerated morbidity and mortality. Given that deconditioned surgical and heart failure patients share similar cardiopulmonary physiology, we examined whether lower pulse pressure is associated with excess morbidity after major surgery. METHODS: This was a prospective observational cohort study of patients deemed by their preoperative assessors to be at higher risk of postoperative morbidity. Preoperative pulse pressure was calculated before cardiopulmonary exercise testing. The primary outcome was any morbidity (PostOperative Morbidity Survey) occurring within 5 days of surgery, stratified by pulse pressure threshold ≤53 mm Hg. The relationship between pulse pressure, postoperative morbidity, and oxygen pulse (a robust surrogate for left ventricular stroke volume) was examined using logistic regression analysis (accounting for age, sex, BMI, cardiometabolic co-morbidity, and operation type). RESULTS: The primary outcome occurred in 578/660 (87.6%) patients, but postoperative morbidity was more common in 243/ 660 patients with preoperative pulse pressure ≤53 mm Hg{odds ratio (OR): 2.24 [95% confidence interval (CI): 1.29-3.38]; P<0.001). Pulse pressure ≤53 mm Hg [OR:1.23 (95% CI: 1.03-1.46); P=0.02] and type of surgery were independently associated with all-cause postoperative morbidity (multivariate analysis). Oxygen pulse <90% of population-predicted normal values was associated with pulse pressure ≤ 53 mm Hg [OR: 1.93 (95% CI: 1.32-2.84); P=0.007]. CONCLUSIONS: In deconditioned surgical patients, lower preoperative systemic arterial pulse pressure is associated with excess morbidity. These data are strikingly similar to meta-analyses identifying low pulse pressure as an independent risk factor for adverse outcomes in cardiac failure. Low preoperative pulse pressure is a readily available measure, indicating that detailed physiological assessment may be warranted. CLINICAL TRIAL REGISTRATION: ISRCT registry, ISRCTN88456378.

Comparing methods to identify hip fracture in a nursing home population using Medicare claims.

UNLABELLED: The inpatient principal diagnosis in Medicare claims identified 96% of hip fractures in hospitalized nursing home residents with high rates of confirmation by other claims files. INTRODUCTION: Hip fracture is typically identified in Medicare claims by examining only the principal diagnosis in the inpatient file, but this simple approach might be inadequate for nursing home residents. Our objective was to examine the impact of varied operational definitions for identifying hip fracture hospitalizations in administrative claims data. METHODS: We conducted a retrospective examination of Medicare inpatient and outpatient claims data for dually Medicaid- and Medicare-eligible nursing home residents in 1999 in California, Florida, Missouri, New Jersey, and Pennsylvania (n = 197,514). We determined the number of hip fractures identified in inpatient (Medicare A) diagnoses codes using differing definitions that varied according to whether or not hip fracture was required to be the principal diagnosis and whether or not confirmatory imaging and procedure codes were required to be found in other (Medicare B) claims files. RESULTS: Hip fractures were found in any inpatient diagnosis position in 4,680 subjects, with 4,479 of these found in the principal diagnosis position. With either approach to diagnosis position, confirmatory imaging and procedure codes were identified for 95% of persons hospitalized with hip fracture. CONCLUSION: The principal diagnosis alone will identify 96% of hip fracture diagnoses in hospitalized nursing home residents. Such diagnoses are confirmed at very high rates by other sources of claims data. Researchers may be confident using a simple approach to identifying hip fracture hospitalizations in this population, using inpatient claims alone and interrogating only the principal diagnosis position.

Correction: Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.

A randomised control trial of oral health education provided by a health visitor to parents of pre-school children.

OBJECTIVES: To determine the effect of oral health education carried out by a specially trained health visitor on the dental health of young children. DESIGN AND SETTING: Children, who were recruited during their 8-month distraction-hearing test, were randomly allocated to intervention and control groups. A home visit by the health visitor was arranged to parents in the intervention group who were given dental health advice. A second home visit, when the child was about 20 months old, focused on a completed diet record sheet and discussions about what and when the child was eating and drinking. Children in the intervention group received a toothbrush and toothpaste containing 440 ppm fluoride at both visits while those in the control group received the level of care usually provided by health visitors in the area. The children's teeth were examined when they were three years old and two years later as part of a census survey of 5-year-old children in the area. MAIN OUTCOME MEASURES: The numbers of decayed, missing and filled tooth surfaces. RESULTS: 251 children were recruited to the control group and 250 to the intervention group. At age three, they were examined; the mean dmfs scores were 2.19 (95% Confidence Interval: 1.41-2.97) in the control group (n = 171) and 2.03 (CI: 1.39-2.67) in the intervention group (n = 181). During the census survey 276 of the children in the study were examined at school. At this age the mean dmfs scores were 4.84 (CI: 3.39-6.29) in the control group (n = 129) and 3.99 (CI: 2.54-5.04) in the intervention group (n = 147). However, the mean dmfs of the remaining 2,253 children who were examined was 5.94 (CI: 5.55-6.33). CONCLUSIONS: No statistically significant differences in mean dmfs scores were found between the control and intervention groups of children, although, as the children grew older, the gap between them widened. However, the mean dmfs score of other 5-year-olds in the area was significantly worse than that of children in the intervention group. Asking the control parents to take part in the study and examining their children at three years may have had an effect on their dental health status and have made it more difficult to detect any differences achieved by the programme.

Establishment of imaginal discs and histoblast nests in Drosophila.

In Drosophila the homeotic genes of the bithorax-complex (BX-C) and Antennapedia-complex (ANT-C) specify the identity of segments. Adult segment primordia are established in the embryo as the histoblast nests of the abdomen and the imaginal discs of the head, thorax and terminalia. We have used a molecular probe for the limb primordia and in vivo culture to describe the nature of the adult primordia in mutants in which the pattern of homeotic gene expression was altered. The results suggest that the histoblast or disc 'mode' of development is initiated by the extended germ band stage through activity of the BX-C and ANT-C and is relatively inflexible thereafter [corrected].

Thermoregulatory failure secondary to acute illness: complications and treatment.

We report on six patients in whom hypothermia secondary to acute illnesses, including pneumonia, congestive heart failure, renal failure, drug overdose, and hypoglycemia, developed. Complications that occurred were metabolic acidosis in six patients, altered sensorium in five, bradyarrhythmia in three, and hyperamylasemia in two. All patients failed to demonstrate a shivering response and represent cases of acute thermoregulatory failure. Five of the six patients survived. In the course of treatment, the choice of active or passive rewarming should be based on whether or not normal thermoregulatory mechanisms are intact.

Is warfarin underused in the treatment of elderly persons with atrial fibrillation?

BACKGROUND: Several randomized clinical trials have shown that among patients with atrial fibrillation, warfarin sodium use protects against stroke. Recently, experts have voiced concern about possible underuse of warfarin by practicing physicians. Few studies, however, have quantitated the amount of warfarin underuse. METHODS: We randomly sampled 65 Medicare beneficiaries discharged alive from each of 5 small Pennsylvania hospitals between July 1, 1993, and June 30, 1994, with a discharge diagnosis code for atrial fibrillation. Trained abstractors verified that atrial fibrillation was present at some time during the hospitalization, determined the presence of contraindications to anticoagulation, and identified warfarin or aspirin use at discharge for each patient. An internist used implicit criteria to identify the reason for warfarin nonuse in patients who had none of the explicit contraindications to warfarin and did not receive it. RESULTS: Of 322 charts reviewed, 48 patients were not in atrial fibrillation during the hospitalization, 79 had contraindications to warfarin use, 21 either died or were transferred to another hospital, and 2 were admitted with a complication of warfarin. Of the 172 remaining patients, 76 (44%) underwent anticoagulation. On implicit review of the 96 patients who did not undergo anticoagulation, the internist judged that warfarin would not have been appropriate in 54. After excluding those patients, 76 (64%) of the remaining 118 patients underwent anticoagulation. Patients not receiving warfarin were slightly older (81.6 vs 78.3 years old), but this was not statistically significant after stratifying by hospital. Rates of warfarin use at the 5 hospitals varied widely (32%, 57%, 79%, 82%, 94%; P < .001, chi2 with 4 df). Patients with newly diagnosed atrial fibrillation were not more likely to undergo anticoagulation, nor were patients treated by internal medicine or cardiology specialists. CONCLUSIONS: There may be significant warfarin underuse in some hospitals. Overall, approximately one third of patients with atrial fibrillation for whom it appeared appropriate were not anticoagulated with warfarin. Although the fact that data were not available to or were missed by our review surely justifies some of the underuse, one should recall that even a small amount of underuse may affect a large number of people with this common condition.

Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease?

Prospectively collected data on the incidence of treated hypertensive end-stage renal disease (HT-ESRD) were analyzed to investigate whether the higher rate of HT-ESRD in blacks compared with whites is due to differences in putative ESRD risk factors. The overall age-adjusted relative risks of HT-ESRD for black compared with white residents in the Maryland Regional ESRD Registry (Network 31) Catchment Area were 7.4 (95% confidence interval, 5.9 to 9.4) and 9.9 (95% confidence interval, 7.4 to 13.1) for men and women, respectively. In a population level analysis, race-specific HT-ESRD incidence rates in the black and white populations of 13 regions in Network 31 were related to the prevalence of putative ESRD risk factors in those populations. The latter were estimated from the 1981-1982 Maryland Statewide Household Hypertension Survey. Black populations had a 5.6-fold (95% confidence interval, 3.9 to 8.1) higher unadjusted incidence of HT-ESRD than white populations. The HT-ESRD incidence in a population was also directly related to that population's prevalence of hypertension, severe hypertension, and diabetes mellitus and inversely related to measures of socioeconomic status and mean age at diagnosis of hypertension. When adjusted simultaneously for age, prevalence of hypertension, severe hypertension, diabetes, and level of education, the risk of HT-ESRD was still 4.5 (95% confidence interval, 3.2 to 6.2) times higher for black compared with white populations. Our findings failed to support the hypothesis that race-related differences in the prevalence, severity, or age at onset of hypertension, in the prevalence of diabetes or in socioeconomic status, explain the well-recognized black-white differences in the HT-ESRD incidence.

Understanding racial variation in the use of coronary revascularization procedures: the role of clinical factors.

BACKGROUND: Black patients undergo coronary artery bypass grafting and percutaneous transluminal coronary angioplasty less often than white patients. It is unclear how racial differences in clinical factors contribute to this variation. METHODS: A retrospective cohort study was performed of 666 male patients (326 blacks and 340 whites), admitted to 1 of 6 Veterans Affairs hospitals from October 1, 1989, to September 30, 1995, with acute myocardial infarction or unstable angina who underwent cardiac catheterization. The primary comparison was whether racial differences in percutaneous transluminal coronary angioplasty and coronary artery bypass grafting rates persisted after stratifying by clinical appropriateness of the procedure, measured by the appropriateness scale developed by the RAND Corporation, Santa Monica, Calif. RESULTS: Whites more often than blacks underwent a revascularization procedure (47% vs 28%). There was substantial variation in black-white odds ratios within different appropriateness categories. Blacks were significantly less likely to undergo percutaneous transluminal coronary angioplasty (odds ratio, 0.30; 95% confidence interval, 0.14-0.63 [P<.01]) when the indication was rated "equivocal." Similarly, blacks were less likely to undergo coronary artery bypass grafting (odds ratio, 0.44; 95% confidence interval, 0.23-0.86 [P<.01]) when only coronary artery bypass grafting was indicated as "appropriate and necessary." Differences in comorbidity or use of cigarettes or alcohol did not explain these variations. Using administrative data from the Veterans Health Administration, we found no differences in 1-year (5.2% vs 7.4%) and 5-year (23.3% vs 26.2%) mortality for blacks vs whites. CONCLUSION: Among patients with acute myocardial infarction or unstable angina, variation in clinical factors using RAND appropriateness criteria for procedures explained some, but not all, racial differences in coronary revascularization use.

Dental health of prisoners in the north west of England in 2000: literature review and dental health survey results.

BACKGROUND: A caries prevalence study of prisoners in the North West of England was conducted to allow comparisons with results of the 1998 United Kingdom Adult Dental Health Survey. METHOD: A random sample of prisoners in the North West of England was interviewed and examined using the same criteria as the 1998 United Kingdom Adult Dental Health Survey. RESULTS: From a random sample of 316 prisoners, 279 (88%) were interviewed and 272 (86%) received a dental examination. Prisoners enter prison with twice as many decayed teeth (mean 4.2) than found in the general population in the North West of England (mean 1.9). Prisoners also have fewer restored teeth. There was little difference between the mean DMFT of adult male prisoners and young offender male prisoners. There was little difference in the mean DMFT of those in prison for more or less than two years. CONCLUSIONS: Prisoners in the North West of England had more decayed or unsound teeth, and fewer restored teeth than both non-institutionalised adults in the North West of England and social classes IV and V in England. Attempts to improve the effectiveness and efficiency of the Prison Dental Service in the North West of England may render the prison population dentally fit more speedily.

How is developmental stability sustained in the face of genetic variation?

The number and arrangement of scutellar bristles on the thorax of Drosophila melanogaster is largely invariant in wild-type stocks. This character therefore appears to be buffered against changes in phenotype, and has previously been described as a canalized character. Mutations that do alter this phenotype increase the variability in bristle number and can reveal otherwise cryptic genetic differences at other loci. This phenomenon is examined and possible mechanisms contributing to stability of this developmental event are discussed, but the notion that the character is canalized is found not to be heuristic.

Oscillopsia and tolerance to retinal image movement in congenital nystagmus.

PURPOSE: To determine the relationship between retinal image movement (RIM) and oscillopsia in subjects with idiopathic congenital nystagmus (CN). METHODS: Eye movements were recorded using an IRIS infrared system. The eye movement signal was fed back to move an otherwise stationary target on a screen and thereby modify the RIM experienced by each of the five CN subjects. The target was present with either no background (the absolute condition) or a textured background (the relative condition). Feedback gains were varied from -1.0 (i.e., 100% retinal image increase) to +1.0 (i.e., 100% retinal image decrease or complete stabilization), with 0 representing the zero feedback or stationary target condition. In the first experiment, RIM thresholds were determined for a range of feedback values. Using zero feedback, a second experiment measured the detection threshold for absolute and relative motions to a ramp-generated target movement for five CN and five control subjects. RESULTS: Under feedback control spatial constancy broke down for both increased and reduced RIM. The range of spatial constancy was greater for absolute (-0.56 to +0.44) compared with relative (-0.18 to +0.18) RIM. Motion detection thresholds for the CN group were 8 times less sensitive to the absolute and 17 times less sensitive to the relative motion of the target compared with the control group. CONCLUSIONS: These results suggest that in CN subjects perceptual stability is achieved primarily by extraretinal signals.

Short- and long-term responses to diltiazem in patients with variant angina.

Short- and long-term effects of diltiazem on angina frequency were studied in 12 patients with variant angina (pain at rest with S-T elevation). Each patient first entered a double-blind short-term trial. Either diltiazem, in two dosage schedules (120 and 240 mg/day), or placebo was administered in a randomized double-blind program over 10 weeks. Significant decreases in frequency of angina were observed when diltiazem treatment periods were compared with placebo periods. Six patients were asymptomatic, one had 50 percent or greater decrease, and two had a smaller decrease in angina frequency. Two patients showed no important improvement during short-term diltiazem therapy. One patient experienced ventricular fibrillation in the placebo period and was advanced to treatment with open label diltiazem before responses could be ascertained in the double-blind trial. All other patients were then advanced to open label diltiazem therapy and followed up for an average of 16 months (range 8 to 23). Responses during the short-term trial accurately predicted responses during long-term therapy. Of the six patients who were asymptomatic during short-term therapy, five remained asymptomatic and one had rare episodes of angina. One other patient continued to have a good response (50 percent or greater decrease in angina frequency) and two other patients had a partial response. The two patients who did not respond during short-term therapy did not respond during long-term therapy.

Regional coronary hemodynamic responses to cold stimulation in patients without variant angina.

The responses to cold in patients with exertional chest pain were studied by measuring coronary sinus and great cardiac vein flows, aortic and left ventricular pressure and diameters of epicardial and small (0.4 to 1.0 mm) intramyocardial coronary arteries before and after the left hand of 18 such patients was immersed in ice water. Coronary sinus and great cardiac vein flows were used as indexes of total and anterior left ventricular flows. Coronary sinus flow minus great cardiac vein flow was used as an index of inferior left ventricular flow. Perfusion of left ventricular regions was considered potentially "normal" or "abnormal" according to the presence or absence of 50 percent or greater stenosis of luminal diameter in the coronary artery supplying a given region. With cold stimulation, increases occurred in heart rate (6 beats/min), mean aortic pressure (22 mm Hg) and left ventricular end-diastolic pressure (8 mm Hg) (all p less than 0.05). Left ventricular flow in normally perfused regions increased as resistance decreased. Left ventricular flow in abnormally perfused regions increased slightly and resistance increased. Regional left ventricular flow increased more, and changes in resistance differed in normally and abnormally perfused regions. Coronary arterial diameter decreased only minimally (6 percent) in both normal and abnormal left ventricular regions. These data show that cold stimulation increases coronary resistance in abnormally perfused left ventricular regions. Cold stimulation-related increases in coronary resistance do not appear to be caused by coronary arterial "spasm."

Reevaluation of electrocardiographic criteria for left, right and combined cardiac ventricular hypertrophy.

Cardiac chamber weight was determined at necropsy in 323 men to develop correlative studies of electrocardiographic criteria for ventricular hypertrophy. Thirty recommended criteria for left ventricular (LV) hypertrophy, 10 for right ventricular (RV) hypertrophy, and combinations of both criteria for combined hypertrophy were evaluated. Four methods for electrocardiographic diagnosis of LV hypertrophy were derived: (1) a modification of the Romhilt-Estes point system; (2) the presence of any 1 of 3 criteria: (a) S V1 + R V5 or V6 greater than 35 mm, (b) left atrial abnormality, or (c) intrinsicoid deflection in lead V5 or V6 greater than or equal to 0.05 second; (3) a combination of any 2 criteria or of 1 criterion (above) plus at least 1 of the following 3 additional criteria: (a) left-axis deviation greater than -30 degrees, (b) QRS duration greater than 0.09 second, or (c) T-wave inversion in lead V6 of 1 mm or more; and (4) the use of a single criterion--left atrial abnormality. Sensitivity varied from 57 to 66% and specificity from 85 to 93% among these 4 methods. Myocardial infarction increased sensitivity of the foregoing methods, but the specificity was reduced. Method 2 is preferred for the electrocardiographic diagnosis of LV hypertrophy. Two methods were useful for right ventricular (RV) hypertrophy: (1) the use of any 1 of 4 criteria: (a) R/S ratio in lead V5 or V6 less than or equal to 1; (b) S V5 or V6 greater than or equal to 7 mm; (c) right-axis deviation of more than +90 degrees, or (d) P pulmonale; and (2) use of any 2 combinations of the foregoing criteria. Sensitivity ranged from 18 to 43% and specificity from 83 to 95%. Combined hypertrophy was best diagnosed using left atrial abnormality as the sole criteria of LV hypertrophy, plus any 1 of 3 criteria of RV hypertrophy: (a) R/S ratio in lead V5 or V6 less than or equal to 1, (b) S V5 or V6 greater than or equal to 7 mm, or (c) right axis deviation greater than +90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Medicare claims data to evaluate outcomes in elderly patients undergoing lung resection for lung cancer.

OBJECTIVE: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. DESIGN: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (part A) claims records to identify patients who underwent lung resection for lung cancer; we assessed perioperative, one-year, and two-year survival using Medicare enrollment file data. PATIENTS: From a nationally random sample of 1,138,000 Medicare beneficiaries over 65 years of age, we identified 1,290 individuals who fulfilled our definition for lung resection for lung cancer. MEASUREMENTS AND MAIN RESULTS: Overall perioperative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced perioperative and one-year and two-year survival. The adverse effect of advanced age on one-year and two-year survival following lung resection was not explained by the lower life expectancy of older individuals. CONCLUSIONS: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected outcomes vary with the patient's age, sex, and the type of surgical procedure performed.

The nature of head postures in congenital nystagmus.

We investigated the factors that determine the nature and extent of abnormal head postures in patients with congenital nystagmus. The head positions and eye movements of 16 patients were monitored while they adopted a variety of gaze positions. Five patients displayed a single head posture and four displayed multiple head postures. Six of the nine head postures matched the minimum intensity zone. The extent of the head posture was also found to be dictated by the velocity distribution of the slow phase, the nystagmus beat direction, and the neutral zone. Our results suggest that the surgical management of a head posture should not always be based only on the relocation of the minimum intensity zone to the primary gaze position.