Administrative incidence of psychosis assessed in an early intervention service in England: first epidemiological evidence from a diverse, rural and urban setting.

BACKGROUND: Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural-urban population. METHOD: A population-based study of FEP (ICD-10, F10-39) in people aged 17-35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings. RESULTS: A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5-56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1-3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization. CONCLUSIONS: Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.

Cognitive behaviour therapy for improving social recovery in psychosis: a report from the ISREP MRC Trial Platform Study (Improving Social Recovery in Early Psychosis).

BACKGROUND: This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment. The study was a single-blind randomized controlled trial (RCT) with two arms, 35 participants receiving cognitive behaviour therapy (CBT) plus treatment as usual (TAU), and 42 participants receiving TAU alone. Participants were assessed at baseline and post-treatment. METHOD: Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome. The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions. The primary outcomes were weekly hours spent in constructive economic and structured activity. A range of secondary and tertiary outcomes were also assessed. RESULTS: Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes. However, analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale (PANSS) [F(1, 69)=3.99, p=0.05]. Subsequent exploratory analyses within diagnostic subgroups revealed clinically important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis. CONCLUSIONS: The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients. However, planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems. These promising results need to be independently replicated in a larger, multi-centre RCT.

Micro-CT for saw mark analysis on human bone.

In toolmark analysis, microscopy techniques, such as micro-CT, are used to visualise and measure toolmarks left on bones by a tool. In dismemberment cases, properties such as the width of the saw mark can provide cues to which tool was used by the culprit. The aim of the current study was to establish whether; (i) micro-CT is an appropriate imaging technique for saw mark analysis, (ii) toolmarks statistically differ when created with different tools, (iii) toolmark width can predict tool blade width, and (iv) toolmarks differ if created under different methodological conditions. Across two experiments, 270 saw marks were created using eight tools with either a controlled or free saw action on either fleshed or defleshed human long bone. Toolmarks were micro-CT scanned and seven toolmark properties were categorised or measured by two independent raters. The current study found that; (i) micro-CT was found to be a powerful and reliable imaging method for the visualisation and measurement of saw mark properties, (ii) toolmark properties differed significantly within and between various methodological conditions (p<.001) when created by eight different tools, (iii) a regression model developed using toolmark widths from Experiment 2 overall predicted 94% of tool widths in Experiment 1, and iv) methodological factors such as tissue presence and saw action significantly and inconsistently influenced toolmark properties for different tools. The study further validates the use of mirco-CT for saw mark analysis and demonstrates the potential of using toolmark properties to determine the tool used in cases of dismemberment. Given the effects that methodological factors such as tissue presence can have on toolmark properties, future studies should use experimental set ups with fleshed human tissue and use a free saw action.

Effects of a maternal high-fat diet on offspring behavioral and metabolic parameters in a rodent model.

Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.

The 4 Questions to Ask and Answer Regarding ICD-10: Second of a 2-Part Series.

INTRODUCTION: On October 1, 2015 the United States will transition from the decades-old 9th revision of the International Classification of Diseases (ICD-9) set of diagnoses for coding medical encounters and inpatient procedure codes to the far more contemporary, vastly larger and much more detailed 10th revision of those code sets (ICD-10). In this second part of a 2-part series we will address the 2 remaining questions about this transition, namely why you should check your codes to ensure correct coding and how to best prepare for the transition. METHODS: A search was undertaken to determine how ICD-10 codes are organized and the best techniques to choose correct codes, and how to best prepare for the transition. Results were based on this search, and on input and expertise from coding experts as well as personal experience. RESULTS: Due to the significant change in the code set and rules, ICD-10 codes should be double-checked for accuracy, especially early in the transition, as finding the most accurate code involves challenges. Detailed preparation of all aspects of the practice potentially affected by ICD-10 codes is vital. CONCLUSIONS: The transition from ICD-9 to ICD-10 will have a major impact on anyone who uses health care information. Proper preparation is vital to a smooth transition.

The 4 Questions to Ask and Answer Regarding ICD-10: First of a 2-Part Series.

INTRODUCTION: On October 1, 2015 the International Classification of Diseases and Related Health Problems, 9th revision (ICD-9) will be replaced by the 10th revision (ICD-10) for coding medical encounters in the United States. This transition will fundamentally change how medical care is documented, how health care is delivered and how delivery systems operate. We will shed light on the ICD-10 transition and answer 4 questions we believe to be important to this transition. We first wanted to know 1) how ICD-10 differs from ICD-9 and 2) why we need to do this/what frustrations we might expect. METHODS: A search was undertaken regarding the transition from ICD-9 to ICD-10, and included input and expertise from coding experts as well as personal experience. RESULTS: ICD-10 differs from ICD-9 in a number of ways, not just in the extreme expansion in the number of codes and specificity. ICD-10 has a new structure and rules that must be understood. The proposed advantages of transitioning to ICD-10 include a better analysis of disease patterns, improved treatment outcomes, streamlined claims submissions and reduced overall health care costs. These "advantages" have been debated and not yet proved. The transition could be very expensive and very frustrating. CONCLUSIONS: The transition to ICD-10 presents a significant implementation challenge for every health care provider and practice, and could be financially devastating to those who are unprepared. There is a significant cost to implementation, much of which is seemingly placed directly on health care providers. We must be prepared.

Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

Phenobarbital pharmacokinetics in neonates.

Phenobarbital pharmacokinetics after intravenous injection were studied in 8 neonates with seizures. Subjects ranged in gestational age from 30 to 40 wk. Plasma concentrations of phenobarbital were measured by enzyme-multiplied immunoassay (EMIT). The volume of distribution (Vd) of phenobarbital was 0.97 +/- .15 L/kg which was independent of the dose administered. Vd and gestational age did not correlate. Phenobarbital clearance calculated from average concentrations in patients maintained on phenobarbital for 1 to 4 wks was consistent, with a decrease in t1/2 from 115 hr after 1 wk to 67 hr after 4 wk of therapy. The elimination of phenobarbital decreased at an exponential rate with a t1/2 of 4.6 days. A pharmacokinetic model with an exponentially increasing elimination rate term was used to describe the data. Average concentrations predicted with the use of the model corresponded adequately with experimental results. The increases in clearance observed are thought to be related to rates of turnover of drug-metabolizing enzymes in the neonate.

Effect of glycerol and hyperosmolality on intracranial pressure.

Glycerol has been used in cerebral edema for hyperosmolar dehydration of brain tissue, but only empirical relationships govern this use. Since the efficacy of treatment with glycerol would likely increase with data on the relationship between drug blood levels and intracranial pressure (ICP), we examined the clinical pharmacology of the drug. Plasma samples were assayed for glycerol by a new method using gas chromatography with a flame ionization detector. Data were collected from 12 children who were in Children's Hospital of Pittsburgh (CHP) and who had cerebral edema of differing etiology that was treated with glycerol; they were monitored by intraventricular catheter. Glycerol was infused according to CHP guidelines. ICP reduction correlated with glycerol concentration and plasma concentrations of 1 to 3 mg/ml (10 to 30 mOsm/ml) were necessary to maintain an ICP below 20 torr. The relationship between osmolality and plasma glycerol level was also examined; there was good correlation between the idiogenic osmolality and drug concentration. Our studies support the clinical observations that relatively high doses of glycerol (0.2 to 1.0 gm/kg/hr), leading to plasma concentrations of 10 to 30 mOsm/l, are necessary to control ICP in patients with cerebral edema. Glycerol blood levels may be estimated from serum osmolality.

Cerebrovasculopathy following irradiation in childhood.

Symptomatic intracranial vasculopathy developed in four patients following irradiation for central nervous system tumors. All the patients presented with a stroke-like picture from 2 to 22 years after the completion of radiotherapy. Two of the patients showed abnormalities on arteriography consisting of narrowing of the supraclinoid portion of the internal carotid artery and the adjacent proximal anterior and middle cerebral arteries. Although the risks of radiotherapy for central nervous system tumors of malignant potential are outweighed by potential benefit, the risks should be carefully considered in cases of tumors with little or no malignant potential.

Phenobarbital and phenytoin in neonatal seizures: metabolism and tissue distribution.

Loading doses of 15 to 20 mg per kilogram of both phenobarbital and phenytoin, administered intravenously, are necessary in the newborn to achieve rapid therapeutic plasma anticonvulsant levels. Maintenance doses of 3 to 4 mg per kilogram of both agents will maintain therapeutic levels. Phenytoin is, however, not predictably absorbed by the oral route. Brain:plasma ratios were 0.71 +/- 0.21 for phenobarbital and 1.28 +/- 0.32 for phenytoin, which are in general agreement with reported adult values. The brain:plasma ratio of phenobarbital increased with gestational age. Phenytoin was found in higher concentration in gray matter, whereas phenobarbital was equally distributed between gray and white matter.

Biotinidase deficiency: accumulation of lactate in the brain and response to physiologic doses of biotin.

Biotinidase deficiency is the most common cause of late onset, biotin-responsive multiple carboxylase deficiency (MCD). We studied the two oldest known boys with this disorder who had high CSF content of lactate that could have contributed to the clinical disorder. The symptoms of these patients implied that near physiologic, rather than pharmacologic, doses of biotin may be sufficient for treatment.

Childhood oligodendrogliomas presenting with seizures and low-density lesions on computed tomography.

Three children with cerebral oligodendrogliomas causing partial complex or generalized seizures presented with completely normal neurologic examinations. CT showed low-density, nonenhancing surface lesions. Although these CT features are usually associated with infarcts or cysts, neoplasm was suspected because of irregularity of the margins and erosion of the adjacent inner table of the skull. Oligodendrogliomas often enlarge slowly and may cause seizures years before they produce focal neurologic signs. CT of all children with seizures not responsive to anticonvulsant medication and focal clinical or EEG abnormalities will hasten diagnosis of slowly growing intracranial mass lesions.

Basilar impression in children.

Ataxia is a common neurologic sign in childhood. Basilar impression due to bony abnormalities of the craniovertebral junction is an uncommon but readily treatable cause of ataxia in children. Two children who had neck stiffness, ataxia, nystagmus, and corticospinal tract signs are described. Basilar impression was recognized only after specific radiologic studies were performed. Both children were treated surgically with good results.

Pontosubicular necrosis and hyperoxemia.

Pontosubicular necrosis (PSN) is confined to a short perinatal developmental period and is apparently related to asphyxia at birth. Neuronal necrosis with karyorrhexis and proliferative changes in astrocytes are most prominent in the pontine gray matter and subiculum of the hippocampus. We have observed a striking association of PSN in neonates with high arterial blood oxygen (PO2) levels during the first week of life. All autopsies performed on neonates in 1977 at Magee-Womens Hospital (University Health Center of Pittsburgh) were reviewed, and all 64 neonates who survived long enough to have multiple PO2 determinations were studied. All had severe hypoxia, respiratory distress, and/or apnea. Twenty-seven (group I) did not have PO2 levels higher than 150 torr whereas 37 (group II) had PO2 levels higher than 150 torr for a sustained period. PSN was not seen in group I; it was prominent in group II. PSN was most severe between the gestational ages of 26 to 36 weeks. Hyperoxemia may decrease cerebral blood flow selectively at this critical phase of development or there may be a greater sensitivity to the toxic action of high blood oxygen levels in the presence of acidosis and hypoxia. A combination of these factors seems most probable.

Epidural abscess and vertebral osteomyelitis following serial lumbar punctures.

Lumbar epidural abscess and vertebral osteomyelitis were diagnosed in a 3-month-old infant, born prematurely, who had had repeated lumbar punctures for the treatment of posthemorrhagic hydrocephalus. Staphylococcus aureus was the causative organism. Successful treatment was achieved with 6 weeks of intravenous antibiotics without surgical drainage. Infectious complications of lumbar punctures are rare, but may occur when multiple punctures are attempted in small premature infants whose subarachnoid space contains large amounts of blood. Infection can be introduced directly by a contaminated spinal needle, or trauma to the tissues with bleeding can create a favorable site for bacterial adherence and multiplication. Posthemorrhagic ventricular dilation often resolves spontaneously and serial lumbar punctures should be used to treat this condition only when CSF flow is easy to establish and maintain.

Destructive brain lesions of presumed fetal onset: antepartum causes of cerebral palsy.

Antepartum events have been associated with fetal brain injury and may contribute to later neurological sequelae. However, children with these injuries may be asymptomatic or exhibit few clinical signs during the neonatal period. Six neonates are presented with destructive brain lesions of fetal onset based on radiological and neurophysiological studies at birth. No intrapartum difficulties were noted in any of the cases. Two maternal histories were significant for either placental bleeding or toxemia during the second or third trimesters of pregnancy. Fetal porencephaly from presumed intraventricular hemorrhage was documented by serial abdominal sonography for these two children. No causes could be assigned for the remaining four patients with destructive brain lesions. All six children had normal results on neurological examinations at birth, although four neonates later presented with isolated seizures at 8 to 30 hours of life which resolved after administration of anti-epileptic medication. In all cases initial neonatal electroencephalographic records showed abnormalities consisting of major background asymmetries or seizures. Initial documentation of cerebral lesions was made by fetal sonography (two patients) and computed tomography scan (four patients) during the initial 30 hours of life, timing the lesions to the antepartum period. Cerebral palsy has been documented in all children; one child had resolution of her deficits by 6 months of age. Better surveillance of events during the antepartum period may help identify specific pathophysiological conditions that contribute to cerebral palsy. Neurophysiological and imaging studies should be used during the immediate new-born period for neonates believed to have cerebral lesions based on maternal sonography or isolated seizures.

Intracerebral hemorrhage in the full-term neonatal infant.

Supratentorial intracerebral hemorrhage was diagnosed in 18 full-term neonates, including six with primarily intraparenchymal hemorrhage and 12 with primarily intraventricular hemorrhage. Precipitating or associated factors were hypoxic-ischemic injury in five patients, polycythemia in two, and cranial birth trauma in two. Nine other infants had no identifiable medical risk events. The pathogenesis of intraparenchymal hemorrhage was probably related to hemorrhagic infarction, but the pathogenesis of intraventricular hemorrhage was often unknown. All 17 survivors returned for neurologic and developmental examinations between 1 and 7 years of age. Follow-up assessments were normal in nine children and abnormal in eight. Two had perceptual difficulties, three had moderate-to-severe cognitive deficiencies (two of the three had hemiplegia), and three had severe mental and neurologic handicaps. Eight of nine children with known or suspected hypoxic-ischemic or traumatic insults suffered moderate-to-severe disabilities whereas eight of nine children with no known precipitating cause for their hemorrhage developed normally.

Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae.

Electrographically confirmed seizures in preterm and term neonates were compared with respect to clinical correlates, incidence, associated brain lesions, and risk for neurologic sequelae. Over a 4-year period, 92 neonates from a neonatal intensive care unit population of 4020 admissions at a large obstetric hospital with 40,845 livebirths had electrographically confirmed seizures. Sixty-two neonates were preterm and 30 were full-term for gestational age. Chi-square calculations were used to compare the two groups. While the incidence of seizures for all neonates admitted to a neonatal intensive care unit was 2.3%, outborn neonates were more likely to have seizures than inborn neonates. Preterm neonates of < or = 30 weeks gestational age had a seizure frequency of 3.9%, which was significantly higher than that of older preterm neonates and full-term neonates. Clinical criteria contemporaneous with electrographic seizures were noted in only 28 (45%) of 62 preterm, and 16 (53%) of 30 full-term neonates. Subtle seizures coincident with electrographically confirmed seizures were the most predominant clinical type for both term and preterm neonates (71% and 68%, respectively). The distribution of clonic, myoclonic, and tonic seizures was also similar for both groups. Autonomic signs coincident with electrographically confirmed seizures (ie, blood pressure, heart rate, oxygenation, respiration changes) were more frequently observed in preterm than full-term neonates with subtle seizures; 7 (37%) of 19 compared with 1 (6%) of 16. Electrical seizures without clinical correlates were noted more frequently than electroclinical seizures for both populations.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency of bleeding and height of adolescent haemophiliacs.

The relation between the height of adolescent haemophiliacs and their bleeding frequency has been studied. 45 haemophiliacs aged 10--19 years were divided into 3 groups: small, medium and tall, using a Height Standard Deviation Score. The average bleeding frequency per 100 days in the group of small haemophiliacs was 8.71 +/- SD 4.47, in the medium height group 10.18 +/- SD 6.71, while the tall individuals bled in average 15.97 +/- SD 3.15 every 100 days. There was no relationship between age and bleeding frequency.