The Predictive Value of the G8 Questionnaire in Older Patients with Lung Cancer or Mesothelioma before Systemic Treatment.

AIMS: The standard evaluation of older lung cancer or mesothelioma patients for systemic anti-cancer treatment, based on performance status, is inaccurate. We used the G8 questionnaire to assess a patient's fitness for chemotherapy and explored the correlations between G8 scores, treatment decisions and clinical outcomes. MATERIALS AND METHODS: In total, 201 older patients (≥70 years) with advanced lung cancer or mesothelioma were prospectively assessed by standard clinical methods and a G8 questionnaire. Treatment decisions before and after reviewing the G8 score were documented. Patients were divided into low (<11), intermediate (11-14) and high (>14) G8 score groups. Patients' characteristics, treatment plans and clinical outcomes among each G8 score group were compared. Similar analyses were compared between good (<2) and poor (≥2) performance status. RESULTS: 10.1% of patients' treatment plans changed after oncologists reviewed G8 scores. The G8 score correlated inversely with performance status. More patients with low G8 scores (22.5%) were offered the best supportive care compared with 4.5% in intermediate and 1.9% in high G8 score groups. More patients (30.1%) with low G8 scores had treatment changed from chemotherapy to best supportive care on the planned day of their treatment, compared with intermediate (7.5%) and high (6.1%) G8 score groups. High G8 score patients received higher chemotherapy intensity and survived longer than patients with intermediate or low G8 scores. CONCLUSIONS: The G8 score with two cut-off values can predict functional status, chemotherapy tolerability and prognosis in older patients with lung cancer or mesothelioma, thus supporting oncologists on treatment decisions for this population.

Neurocognition and conversion to psychosis in adolescents at high-risk.

This study examined neurocognitive predictors of conversion to Axis I psychosis among adolescents at high-risk for psychosis (AHRP). There were no significant differences in neurocognitive performance between adolescents at high-risk for psychosis who converted (AHRP+) and adolescents at high-risk for psychosis who did not convert (AHRP-). Within-sex comparisons revealed a relation between risk status and performance among females, with AHRP+ performing below AHRP-, but this effect did not hold for males. Between-sex comparisons revealed AHRP- males performed worse than AHRP- females on several measures. Across groups, males performed better than their female counterparts on select measures. Results are discussed in terms of implications for use of neurocognitive profiles as bio-risk markers of psychosis, while considering sex differences.

Developmental changes in cortisol secretion in normal and at-risk youth.

Adolescence is associated with an increase in the rate of certain psychiatric symptoms, and it is typically the developmental period when prodromal features of the major psychiatric disorders emerge. This is especially true of schizophrenia, with the majority of patients showing a marked postpubertal rise in schizotypal signs that predates the onset of clinical symptoms in early adulthood. Cross-sectional studies of youth have revealed a positive correlation between age and saliva cortisol level, suggesting a normative maturational increase in activity of the hypothalamic-pituitary-adrenal (HPA) axis. It has been hypothesized that this increase may trigger the expression of symptoms in vulnerable individuals. The present longitudinal study measured cortisol secretion and its relation with symptom development in samples of youth with schizotypal personality disorder (SPD), other personality disorders, or no Axis II disorder. The findings indicate moderate stability in cortisol levels across a 2-year period, with a longitudinal increase in cortisol levels over time. Cortisol levels at the first and second assessments were correlated with the severity of SPD symptoms at follow-up. The results are consistent with the notion that the HPA axis undergoes a postpubertal maturational process that moderates the expression of psychiatric symptoms.

Cognitive functioning, cortisol release, and symptom severity in patients with schizophrenia.

BACKGROUND: There is substantial evidence of dysregulation of cortisol secretion, hippocampal abnormalities, and memory deficits in schizophrenia and other psychotic disorders. Research also suggests that cortisol secretion augments dopaminergic activity, which may result in increased symptom expression in this clinical population. METHODS: We examined the relations among cortisol release, cognitive performance, and psychotic symptomatology. Subjects were 18 adults with schizophrenia or schizoaffective disorder, seven with a nonpsychotic psychiatric disorder, and 15 normal control subjects. Tests of memory and executive function were administered. Cortisol was assayed from multiple saliva samples. RESULTS: Findings indicated the following: 1) patients with psychotic disorders scored below the comparison groups on the cognitive measures; 2) for the entire sample, cortisol levels were inversely correlated with performance on memory and frontal tasks; and 3) among patients, cortisol levels were positively correlated with ratings of positive, disorganized, and overall symptom severity, but not with negative symptoms. CONCLUSIONS: The present results suggest that abnormalities in the hypothalamic-pituitary-adrenal axis and hippocampal systems play a role in observed cognitive deficits across populations. Among psychotic patients, elevated cortisol secretion is linked with greater symptom severity.

Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases.

BACKGROUND: Some studies have reported psychotic symptom exacerbation during "pharmacologic challenge" paradigms using dopamine agonists. Few studies, however, have examined the effects of these agonists on neurocognitive functions in patients with schizophrenia. This study assessed the effects of methylphenidate infusion on an oral word production test with demonstrated sensitivity to frontal lobe lesions, and on clinical state. METHODS: Patients were tested at two different phases; at the onset of their first-episode of schizophrenia (acute phase), and then again after they had responded to treatment and were clinically stable (stabilization phase). During each phase, patients were tested prior to and following methylphenidate infusion. Symptom clusters (i.e., positive, negative, and disorganization) were formed from SANS and SADS-C (+PD) ratings at each of these four timepoints. RESULTS: Patients produced significantly more words at preinfusion and while stabilized, suggesting that overall, decreased dopamine activity was associated with better word production. Redundant errors (i.e., perseverations of previously mentioned words and production of multiple words with the same roots) increased significantly following infusion in the stabilized phase. Disorganization symptoms increased significantly following infusion, regardless of study phase. CONCLUSIONS: These findings are consistent with previous theoretical and empirical findings relating dopamine activity to verbal output, a "redundancy bias" in cognitive control, and exacerbation of disorganization symptoms.

An initial assessment of the Veterans Affairs occurrence screening program.

The Department of Veterans Affairs (VA) established a computerized occurrence screening program in its medical centers in October 1988. Data collected from these hospitals suggest that occurrence screening has been a useful component of the VA's overall quality assurance effort; opportunities for improvement were found in 4.2% of all occurrences. When asked to name the three most effective criteria, there was strong agreement among participating hospitals--50% or more of the facilities ranked readmissions, death, and admission within three days of an unscheduled outpatient visit as the most effective. A majority of facilities (56%) named occurrence screening as one of the more effective elements in identifying quality-of-care issues. These findings must be balanced against important limitations of the occurrence screening process; however, guided by the data it collected, the VA has recently made several changes in its occurrence screening program to address these limitations.

Caisson disease of bone.

Caisson disease of bone, which may affect compressed air workers and divers, is characterized by regions of bone and marrow necrosis that may lead to secondary osteoarthrosis of the hip and shoulder joints. A review of the pathologic, radiologic, and clinical aspects demonstrated uncertainties in the exact etiology. Early diagnosis is often not possible because of the delayed appearance of radiologic abnormalities. Research into these two aspects of this condition was carried out by the Medical Research Council Decompression Sickness Research Team in Newcastle upon Tyne over a ten-year period (1972 to 1982). Because no suitable animal model exists for the study of this condition, bone and marrow necrosis was produced by embolism of bone blood vessels with glass microspheres. With this model, it was shown that the presence of bone and marrow necrosis could be detected by bone scintigraphy using 99mTc-MDP and by measuring changes in serum ferritin concentration at a much earlier stage than was possible by radiography. However, only the former method has proved useful in clinical practice. Investigations into the etiology of caisson disease of bone have shown evidence for an increase in marrow fat cell size resulting from hyperoxia. This phenomenon may play a role in the production and localization of gas bubble emboli, which are thought to be the cause of the bone and marrow necrosis.

Immunoperoxidase staining of previously stained tissue.

Using an unlabelled antibody peroxidase-antiperoxidase method, we have demonstrated that certain tissue antigens can be identified in tissue sections previously stained with hematoxylin and eosin. This technique is useful in identifying antigens in tissues where insufficient unstained material is available.

Myelopathy associated with decompression sickness: a report of six cases.

Four scuba divers and 2 professional deep sea divers developed spinal cord symptoms due to decompression sickness. Symptoms developed during or immediately after ascent in 4 cases and were delayed in 2. In 2 cases new symptoms appeared during a jet flight. In 4 cases paraparesis was associated with a sensory level in the mid or low dorsal region indicating the thoracic cord as the major site of involvement. In the other 2 cases the clinical findings were suggestive of combined lesions in the lower cervical and lumbar cord. Therapeutic recompression led to improvement in each case. Three cases who were re-examined after intervals of 3 to 7 years each showed residual corticospinal and minor sensory signs. One of these cases met with a violent death 3.5 years after the acute episode; examination of the cord showed multifocal white matter degeneration in the posterior and lateral columns between C7 and T4 with secondary ascending and descending tract degeneration. The mechanism of spinal cord damage in decompression sickness is discussed.

Intra-osseous phlebography and intramedullary pressure in the rabbit femur.

Intra-osseous phlebography and the measurement of intramedullary pressure (IMP) have been used clinically and in experimental animals as qualitative methods of measuring blood flow in the bone. The normal phlebographic appearances in long bones are not clearly understood and the correlation between these appearances and the IMP is not known. The distal femora of 10 anaesthetised rabbits were cannulated percutaneously. The IMP was measured and phlebography performed by injecting a radio-opaque dye (Conray 280). The mean resting IMP was 33 millimetres of mercury with a range of 7 to 81 millimetres of mercury. The rate of elimination of dye from the marrow varied from less than 1 minute to 40 minutes. There was no correlation between the rate of elimination of dye and the IMP. Variation in the medullary phlebographic appearance and in the routes of drainage were noted. We concluded that the wide range of resting values for both techniques suggest that neither is a true measure of blood flow in the bone and that the results of research or clinical investigation using these techniques should be viewed with caution.

A study of old lesions of caisson disease of bone by radiography and bone scintigraphy.

A group of patients were studied 10 years after stopping work in a high-pressure environment. Radiographs of their long bones showed little change during the period, but only two of 12 scintigrams were normal. The 10 abnormal scintigrams contained 18 "hot-spots" which were not always associated with an abnormal radiographic appearance; the findings suggest that some lesions may never become visible on a radiograph. A reactive or repair process associated with these lesions may be prolonged and may not be beneficial, as structural failure of the joint may subsequently occur. Prognosis should therefore be guarded.

Scintigraphy versus radiography in the early diagnosis of experimental bone necrosis, with special reference to caisson disease of bone.

The early diagnosis of caisson disease of bone is hindered by the long delay which must elapse before an abnormality becomes apparent on a radiograph. The possible use of bone scintigraphy for this purpose was investigated. Necrosis of the bone and marrow was produced in rabbits by glass microspheres to simulate persistent gas-bubble emboli and then serial radiographs and scintigrams using 99mTc-diphosphonate were obtained. Regions of necrosis could be detected as "hot-spots" on the scintigrams as early as three weeks after the causative insult, which was many weeks before any abnormality could be detected on the radiographs. Histological examination of excised femora suggested that the scintigraphic abnormality might depend on the new bone formation during a reactive or repair process. It is suggested that scintigraphy may have clinical value in caisson disease.

Regional distribution of circulating microspheres in the femur of the rabbit.

In an attempt to explain the distribution of lesions of caisson disease of bone in the human femur, the regional distribution of circulating microspheres which had been labelled with scandium-46 was studies in the femur of the rabbit. Microspheres with a diameter of 15 microns were equally distributed between the two ends of the bone and between the upper and lower halves of the shaft. However, microspheres with a diameter of 50 microns congregated in the upper end of the femur and in the lower half of the shaft, the two sites most commonly affected by caisson disease. A large percentage of the microspheres in the shaft, especially the larger spheres, were retained in the marrow. It is suggested that the microcirculation of the marrow may act as a filter and that the nature and distribution of its vessels determine the site of impaction of circulating emboli. This would explain why lesions of the shaft mainly affect the medulla of the bone and not the cortex.

Caisson disease of bone: a study of the Göttingen mini-pig as an animal model.

Investigation of the exact aetiology, early diagnosis and prevention of caisson disease of bone has been hindered by the inability to produce, by the use of realistic compression/decompression exposures, truly comparable lesions in animals. Four Gottingen mini-pigs were subjected to repeated exposures to pressures of 27 p.s.i.g. for 6 h over a period of 9 months and decompressed according to standard tables. Two mini-pigs acted as controls. In one animal radiological changes were recognised in the left lower femoral shaft 19 weeks after the exposures were started and subsequent examination of that bone confirmed the presence, at that site, of a lesion which macroscopically and microscopically resembled, in every way, the appearances of those seen in the shafts of long bones in man. It is concluded therefore that, properly used, the mini-pig may be a suitable animal model for the study of this condition in man.

Bone necrosis and urinary hydroxyproline excretion in rabbits.

1. Aseptic necrosis of bone is a serious chronic complication of deep-sea diving and compressed-air work. 2. The changes to the bone which occur in this condition take time to develop to the stage where they cause the radiographic signs of bone necrosis, and consequently there is a delay of some months between the causal incident and the first diagnosis by radiography. 3. As a possible method for the earlier detection of bone necrosis the 24 h urinary excretion of hydroxyproline was measured over a period before and after experimental production of bone necrosis in rabbits by the intra-arterial injection of glass microspheres. 4. Total hydroxyproline excretion rose significantly within a few days of the injection in those rabbits in which there was later shown to be historical evidence of bone necrosis. This rise occurred long before there was any radiographic changes. 5. It is suggested that measurements of urinary hydroxyproline might be used to give an early indication of bone necrosis in man.

Serum ferritin and dysbaric osteonecrosis.

Bone and marrow necrosis has been produced in rabbits. Changes in serum ferritin levels have been measured (with appropriate controls). Results suggest that marrow death is followed by a significant rise in serum ferritin levels. The possiblitiy that this may be of value in the early diagnosis of dysbaric osteonecrosis is discussed.

Aseptic necrosis of bone in a compressed air worker.

This paper reports a detailed examination of three lesions of aseptic necrosis of bone occurring in a man who had worked in compressed air eleven years previously. Although two of the lesions were juxta-articular, in neither had the bone collapsed. Histology of only one similar lesion is reported in the literature (McCallum et al. 1966). Necropsy material is considered, together with radiographs and bone scans of the same lesions taken four years earlier. Similar changes have been shown to occur in commercial divers. On the evidence of this case it becomes clear that radiography is limited in its use and that bone scans as an indicator of repair may be open to misinterpretation. There may be a place for operation before the onset of symptoms in these cases of aseptic bone necrosis.