Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12 904 patients.

BACKGROUND: Children with neurodevelopmental disabilities may be at risk of opioid-induced respiratory depression. We aimed to quantify the risks and effectiveness of morphine nurse-controlled analgesia (morphine-NCA) for postoperative pain in children with neurodevelopmental disabilities. METHODS: We carried out a retrospective cohort study of 12 904 children who received postoperative i.v. morphine-NCA. Subjects were divided into a neurodevelopmental disability group and a control group. Rates of clinical satisfaction, respiratory depression, and serious adverse events were obtained, and statistical analysis, including multilevel logistic regression using Bayesian inference, was performed. RESULTS: Of 12 904 patients, 2390 (19%) had neurodevelopmental disabilities. There were 88 instances of respiratory depression and 52 serious adverse events; there were no opioid-related deaths. The cumulative incidence of respiratory depression in the neurodevelopmental disability group was 1.09% vs 0.59% in the control group [odds ratio 1.8 (98% chance that the true odds ratio was >1)]. A significant interaction between postoperative morphine dose and neurodevelopmental disabilities was observed, with higher risk of respiratory depression with increasing dose. Satisfaction with morphine-NCA was very high overall, although children with neurodevelopmental disabilities were 1% more likely to have infusions rated as fair or poor (3.3 vs 2.1%, χ2P<0.001). CONCLUSIONS: Children with neurodevelopmental disabilities were 1.8 times more likely to suffer respiratory depression, absolute risk difference 0.5%; opioid-induced respiratory depression in this group may relate to increased sensitivity to dose-relate respiratory effects of morphine. Morphine-NCA as described was an acceptable technique for children with and without neurodevelopmental disabilities.

The Prosthodontic Pathway for Patients with Anomalies Affecting Tooth Structure.

There are a number of anomalies that affect the structure of the dental hard tissues which impact upon the form, function and aesthetics of the dentition. Understanding the challenges these conditions pose will enable dentists to manage the functional and aesthetic problems with restorative techniques better. This article will present cases that demonstrate the different conditions, the restorative challenges experienced and a variety of restorative treatments in the management of these conditions. Clinical relevance: Awareness of different anomalies affecting tooth structure that may present to the dental practitioner is necessary. Clinicians should appreciate the specific restorative challenges that may arise in treating such patients and the possible treatment options that may be available.

Estimation of platelet count in unstained peripheral blood smears in comparison with stained smears and evaluation of its efficacy.

Assessment of platelet count is an important diagnostic parameter in haematology. Automated blood cell counters have largely replaced the manual method. However, all abnormal platelet counts are verified in Leishman's stained peripheral blood smear. Platelets also can be identified in the unstained blood smears. The objective of this study is to compare the unstained peripheral blood smears with the stained smears and determination of the effectiveness of unstained smears in the estimation of platelet count. 250 Venous blood samples sent for blood cell counts were analyzed. Platelets were counted in the unstained smear under 100× objective in 10 fields without placing immersion oil and the average number of platelets was calculated. Same smear was stained by Leishman's stain and platelets were counted under 100× objective after placing a drop of immersion oil. Collected data were analyzed for intra-class correlation coefficient (ICC). ICC showed excellent agreement (ICC > 0.85). The unstained smears were found to be as effective as stained smears for platelet count in most of the cases. However, in case of doubt a stained preparation has to be made to confirm the count. The turnaround time was 3-5 minutes compared to 15-20 minutes by stained smear technique, thus this technique may be used as an initial screening method whenever there is large sample load.

Mortality in Patients Treated for Tuberculous Pericarditis in Sub-Saharan Africa

Objective: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. Design: Between 1 March 2004 and 31 October 2004; we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon; Nigeria; and South Africa; and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study; with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression; we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. Results: We obtained the vital status of 174 (94) patients (median age 33; range 14-87 years). The overall mortality rate was 26. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40versus 17; P=0.001). Independent predictors of death during follow-up were: (1) a proven non-tuberculosis final diagnosis (hazard ratio [HR] 5.35; 95confidence interval 1.76 to 16.25); (2) the presence of clinical signs of HIV infection (HR 2.28; 1.14-4.56); (3) co-existent pulmonary tuberculosis (HR 2.33; 1.20-4.54); and (4) older age (HR 1.02; 1.01-1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80; 0.90-3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34; 0.10-1.19). Conclusion : A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africans. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease

Fibrinolysis is amplified by converting alpha-antiplasmin from a plasmin inhibitor to a substrate.

alpha(2)-Antiplasmin (alpha(2)-AP) is the fast serpin inhibitor of plasmin and appears to limit the success of treatment for thrombosis. We examined the mechanisms through which monoclonal antibodies (mAbs) against alpha(2)-AP amplify fibrinolysis. The mAbs RWR, 49 and 77 interfered with the ability of alpha(2)-AP to inhibit plasmin, microplasmin and trypsin. In solution, mAbs 49 and 77 bound to alpha(2)-AP with 5-fold to 10-fold higher relative affinity than mAb-RWR, while mAb-RWR bound with greater avidity to immobilized or denatured alpha(2)-AP. Binding studies with chimeric alpha(2)-APs revealed that none of the mAbs bound to sites in alpha(2)-AP that form putative contacts with plasmin, namely the carboxy terminal lysines of alpha(2)-AP, or the reactive center loop in the serpin domain of alpha(2)-AP. Rather, mAb-RWR recognized an epitope in the amino-terminus of alpha(2)-AP (L(13)GNQEPGGQTALKSPPGVCS(32)) near the site at which alpha(2)-AP cross-links to fibrin. mAbs 49 and 77 bound to another conformational epitope in the serpin domain of alpha(2)-AP. mAbs 49 and 77 markedly increased the stoichiometry of plasmin inhibition by alpha(2)-AP (from 1.1 +/- 0.1 to 51 +/- 4 and 67 +/- 7) indicating that they convert alpha(2)-AP from an inhibitor to a substrate of plasmin. This was confirmed by sodium dodecylsulfate polyacrylamide gel electrophoresis analysis showing cleavage of alpha(2)-AP by plasmin in the presence of these mAbs. In summary, these mAbs appear to act at sites distinct from known alpha(2)-AP-plasmin contacts to enhance fibrinolysis by converting alpha(2)-AP from an inhibitor to a plasmin substrate.

Chlamydia trachomatis in cervical and vaginal swabs and urine specimens from women undergoing termination of pregnancy.

The study was devised to assess the prevalence of Chlamydia trachomatis in endocervical and vaginal swabs and first pass urine specimens from women presenting for termination of pregnancy (TOP) and to evaluate the performance of the tests used, namely the ligase chain reaction (LCR) and the direct fluorescence antibody (DFA) test. Eight hundred and sixty three (91%) of 948 women invited to participate agreed to do so; a complete set of results for all test-site combinations was achieved for 793 (92%). The overall prevalence of C. trachomatis was 8.54% (95% confidence interval [CI]: 7.6-10.5%) with a significant negative association with age. The sensitivity (95% CI) of the LCR test for cervical, vaginal and urine specimens was 97% (93-99%); 94% (88-99%) and 83% (75-92%), respectively. The sensitivity (95% CI) of the DFA test for cervical, vaginal and urine specimens was 93% (87-99%); 92% (86-99%) and 78% (68-88%), respectively. Concordance between the LCR and DFA test results was very high for specimens from the same site. The results indicate that nucleic acid amplification tests are appropriate for screening women seeking TOP and, indeed, other women in early pregnancy. The sensitivity of the LCR test for urine specimens was less, but the high levels of concordance observed between the LCR and DFA test results for urine specimens indicates that this was due to a lower organism load rather than inhibition of the LCR.

Audit of orthopaedic bed utilisation.

Blockage of beds on an orthopaedic ward causes multiple problems; it can result in cancellation of patients or elective surgery, longer waiting lists and a crisis with emergency admissions. This often necessitates 'boarding out' of patients, which is not ideal for optimal patient care. Not all patients on an orthopaedic ward need continuing orthopaedic medical or nursing care and it may be more appropriate for these patients to be managed in a rehabilitation environment. From 1/09/98-30/11/98 data were collected on all patients admitted to an adult orthopaedic ward. Information recorded included the reason for admission, age, diagnosis, surgical procedure, family and social circumstances. In addition, the date when discharge was deemed appropriate was recorded as well as the actual date of discharge. We defined the length of overstay as the time spent in an orthopaedic bed after discharge had been deemed appropriate. There were 621 patients admitted for a total of 3159 bed days. There were 253 elective admissions and 368 emergency admissions. A total of 255 bed days were blocked by 46 patients (41 emergency and 5 elective) accounting for eight per cent of the total bed days. Of these 236 (93%) were due to emergency admissions and 19 (7%) were due to elective admissions, most blocked beds were due to patients who required rehabilitation in either a unit for the young disabled or a geriatric rehabilitation ward.

Electrostimulators for acupuncture: safety issues.

Three representative electrostimulators were evaluated to determine whether they meet the manufacturers' labeled nominal output parameters and how the measured parameters compare with a safety standard written for implanted peripheral nerve stimulators. The pulsed outputs (pulse width, frequency, and voltage) of three devices were measured with an oscilloscope across a 500-ohm resistance, meant to simulate subdermal tissue stimulated during electroacupuncture. For each device, at least two measured parameters were not within 25% of the manufacturer's claimed values. The measured values were compared with the American National Standard ANSI/AAMI NS15 safety standard for implantable peripheral nerve stimulators. Although for two stimulators the pulse voltage at maximum intensity was above that specified by the standard, short-term clinical use may still be safe because the standard was written for long-term stimulation. Similarly, the net unbalanced DC current, which could lead to tissue damage, electrolysis, and electrolytic degradation of the acupuncture needle, was within the limits of the standard at 30 pulses per second, but not at higher frequencies. The primary conclusions are (1) that the outputs of electrostimulators must be calibrated and (2) that practitioners must be adequately trained to use these electrostimulators safely.

Reliability and sensitivity of suicide certification in higher-income countries.

World Health Organization age-, sex-, and cause-specific mortality data for the United States and 19 other democratic higher-income countries were utilized to assess the reliability and sensitivity of suicide certification for purposes of cross-national research. Data are found to be highly reliable across age and sex (rs > 0.92; P < 0.001). Relative discrepancies between official suicide rates (putative lower limits) and projected upper limits vary widely internationally. Austrian and Dutch suicide certification is the most sensitive. Least sensitive is certification for certain subpopulations in Finland, Greece, Ireland, Israel, and the United Kingdom. We recommend similar analyses be performed for routine, low-cost surveillance of suicide data quality, and to guide choice of population groups for multivariate comparative research.

Near-infrared reflected spectroscopy and electroencephalography during carotid endarterectomy--in search of a new shunt criterion.

The aim of this clinical study was to evaluate cerebral oximetry with near-infrared reflected spectroscopy (NIRS) as a monitoring system during carotid endarterectomy. The cross-clamping changes of cerebrovascular hemoglobin oxygen saturation (cereb. O2 satn.) were compared with data from a processed EEG analysis. Using the EEG as the gold standard we try to define a new shunt criterion based on near-infrared spectroscopy. 102 patients were studied. During cross-clamping the percentual decrease of cereb. O2 satn. was calculated. The relation between EEG and cereb. O2 satn. is described in terms of sensitivity and specificity, and is graphically shown in a Receiver Operator Characteristic (ROC) curve. At a cut-off value of 5% decrease or more for the cereb. O2 satn., a sensitivity of 100% was found. However, the specificity was only 44%. Higher cut-off values resulted in a gradual increase of the specificity at the expense of a significant decrease of the sensitivity. In conclusion, improved validation and calibration techniques are necessary before this technique may be used for relevant assessment of cerebral oxygenation during carotid surgery. In particular, in order to define a new shunt criterion, the focal aspect of this new technique is probably one of the limitations.

Death certification in treated cases of presenile Alzheimer's disease and vascular dementia in Scotland.

INTRODUCTION: although death certification data are commonly used in dementia epidemiology, their reliability has been questioned. METHODS: death certificates were available from the Registrar General for Scotland for all patients with Alzheimer's disease/presenile dementia (AD PSD) or vascular dementia (VaD) who had died in Scotland up until 31 December 1994. Primary (immediate and underlying) and contributory causes of death were noted as well as place of death. Occupations of male patients were obtained from death certificates or from case notes and classified according to the Standard Occupational Classification. Bronchopneumonia was considered a non-specific cause of death and specific causes of death were classified as: cardiac disease, dementia, cerebrovascular disease, neoplasms, other vascular diseases and other diseases. Place of death was recorded as psychiatric hospital, district general hospital, nursing home or private residence. RESULTS: death certificates of 398 people who had been treated for AD PSD and 348 who had been treated for VaD were identified. Bronchopneumonia was the most common immediate cause of death in the AD PSD group (70.9%) but less so for the VaD group (51.7%). For both groups place of death was associated with significant differences in pneumonia being reported as the immediate cause of death as well as specific underlying and contributory causes of death. Dementia was recorded for 90.5% of AD PSD patients but for only 49.7% of the VaD group. CONCLUSIONS: Scottish death certificate data significantly underestimate the prevalence of presenile VaD. Changes in patterns of institutional care may affect dementia rates estimated from death certificate data.

Survival in early onset dementia: effects of urbanization and socio-economic deprivation.

We estimated survival of patients with early onset Alzheimer's disease (AD) or vascular dementia (VaD) presenting to psychiatric hospitals in Scotland (1974-1988) and related this to age, gender and socio-economic variables. Hospital records of 1794 early onset dementia patients were reviewed. We identified 451 patients with early onset AD and 384 with VaD. Survival to death was calculated from symptom onset and presentation. Small geographical areas (postcode sectors) were classified by urban/rural category and deprivation score. Five-year survival from presentation of early onset AD was 32% for men and 43% for women compared to 22% for men and 36% for women with VaD. We conclude that increased age at presentation was associated with shorter survival in early onset AD and VaD. Socio-economic deprivation was associated with longer survival in VaD. The effects of urban/rural score were accounted for by the major effects of socio-economic deprivation.

Familial or sporadic clusters of presenile dementia in Scotland: I. Parental causes of death in Alzheimer and vascular presenile dementias.

Between 1974 and 1988, discrete areas within Scotland had unexpectedly high incidences of presenile Alzheimer's disease. To examine whether these clusters might be attributable to 'familial' cases occurring in the same locality, we performed a case-control study of parental cause of death entered on death certificates. Cases comprised (1) 145 presenile Alzheimer's disease patients and (2) 73 vascular dementia patients presenting in Lothian between 1974 and 1988. Two control individuals per case, of the same sex, born in the same registration district, and whose fathers had the same occupation as the case's father, were chosen from birth registration data. Parental death certificates for 131 presenile Alzheimer's disease and 65 vascular dementia cases were located. There was no significant association detected between a diagnosis of presenile Alzheimer's disease and dementia as a parental cause of death (p = 0.25), nor for vascular dementia (p = 0.67). Presenile Alzheimer's disease cases were less likely to have a parent die with cerebrovascular disease (chi 2 = 4.80, p < 0.05) and vascular dementia cases more likely to have a parent die with cerebrovascular disease (chi 2 = 5.28, p < 0.05). There was no increased incidence of other vascular disease or bronchogenic carcinoma in cases' parents compared with control individuals' parents.

Familial or sporadic clusters of presenile Alzheimer's disease in Scotland: II. Case kinship.

Clusters of high incidence areas of presenile Alzheimer's disease were found in Scotland between 1974 and 1988. We present a novel index of case kinship based on the number of observed common ancestors of cases compared with the number expected in order to evaluate whether these cluster are attributable to familial cases. One county with high incidence was Lanarkshire, with 69 of the 451 national presenile Alzheimer's disease cases and 185 of the 1794 any-cause dementia cases. None of the 69 presenile Alzheimer's disease cases shared a common great-grandmother and there was no instance where an individual case's great-grandmother was another case's grandmother. Five pairs of dementia cases shared a great-grandmother; for two pairs, one case's great-grandmother was another's grandmother. We estimated the 'at-risk' ancestral population as 46,000 for the midpoint census of 1861 for the cross-sectional estimate, 155,812 for the cumulative estimate between 1831 and 1891, and 90,282 for the cumulative estimate between 1841 and 1871. Hence, we expected a maximum of 0.29 shared great-grandmothers for presenile Alzheimer's disease cases, and 2.13 shared great-grandmothers for dementia cases. Case-kinship is 2.35 more than expected (estimated range 1.84-3.18). We conclude that familial factors contribute to the incidence of dementia in Lanarkshire.

Epidemiology of presenile Alzheimer's disease in Scotland (1974-88) I. non-random geographical variation.

BACKGROUND: Factors that determine geographical differences in incidence rates of 'probable' presenile Alzheimer's disease (AD PSD) may help to clarify the possible role of the environment in its aetiology. METHOD: We have ascertained the treated incidence of AD PSD in Scotland by scrutiny of hospital cassenotes and searched for cases outside hospital settings. Small area geographical analysis compared the observed distribution of cases (each allocated to one of Scotland's 898 postcode sectors) with the estimated random distribution of cases. RESULTS: There was non-random geographical distribution of AD PSD but not of the comparison conditions (vascular dementia (VaD), motor neurone disease, prostatic or ovarian cancers). Substantial differences between Scottish regions were probably not attributable to methodological artefact, as other techniques of case finding showed the same regional differences. CONCLUSIONS: The observed differences in incidence of AD PSD between Scotland's regions are real and some localities have a higher incidence, mostly in central Scotland.

Epidemiology of presenile Alzheimer's disease in Scotland (1974-88) II. Exposures to possible risk factors.

BACKGROUND AND METHOD: We related geographical variation of 'probable' presenile Alzheimer's disease (AD PSD) to exposures to possible risk factors for AD PSD and vascular dementia (VaD) and to geographical differences in survival times after presentation with AD PSD. RESULTS: We found that an ecological measure of socio-economic deprivation was related to VaD but not to AD PSD. Among men with AD PSD and VaD, specific occupations conveyed no altered risk but having fathers who were coal miners was associated with AD PSD and VaD in offspring. Increased paternal age was associated with AD PSD but only in men. These factors acted independently of one another and did not distinguish between geographical areas of high and low incidence. CONCLUSIONS: The length of survival after presentation with AD PSD distinguished between these areas, and when migration between these areas was taken into account, a plausible multifactorial model of the harmful effects of environment emerged, which acted independently of risk factors acting earlier in life.

Case report: granulocytic sarcoma of the small bowel--a rare presentation of leukaemia.

Granulocytic sarcoma (GS) is a local tumour mass that is associated with acute leukaemia. It may present simultaneously with leukaemia or may rarely predate it. The following case demonstrates the radiological features of GS and the importance of its recognition in the treatment.

Ischaemic colitis in association with sigmoid carcinoma: a report of two cases.

The association of ischaemic colitis with a distal obstructing carcinoma is described in two patients. When a segment of colonic ischaemia is demonstrated on barium enema, it is important to consider an association with a distal tumour.