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The five Cs of choice. Outcome measures for individuals with severe and persistent mental illness.

In a time when mental health service providers are cutting costs and services, stakeholders need adequate information in the form of outcome measures to evaluate services based on quality. Outcome measures are particularly important for high-risk populations, where severe and persistent mental illness results in serious functional impairment of daily life. A client-oriented method of gauging rehabilitation of real-world behavior over the long-term, as well as the short-term, and which allows for comparison with other programs, must be developed. Lack of agreement on the domains to be measured, however, has hindered the development of common standards, making it difficult to track accountability and service effectiveness. Four authors provide a framework to help organizations choose and develop appropriate outcome measures, as well as core data suggested to measure longitudinal changes in rehabilitation.

Chronic Disease↗

Immunohistochemical studies on the endotoxin-induced uveitis.

OBJECTIVE: To investigate the longitudinal changes of macrophages and major histocompatibility complex (MHC) class II-positive cells in the iris and ciliary body of Lewis rats after lipopolysaccharide (LPS) injection. METHODS: Immunohistochemistry was performed using monoclonal antibodies to monocytes and macrophages (ED1) and MHC class II-positive cells (OX6) on wholemounts of the iris and ciliary body in endotoxin-induced uveitis (EIU). RESULTS: A network of macrophages (ED1+ cell) and MHC class II-positive cells, was present in the iris and ciliary body of normal Lewis rats. Most cells in the iris and ciliary body displayed dendritiform appearance. A severe involvement of the iris and ciliary body, as evidenced by a rapid influx of monocytes and macrophages and remarkable increase of MHC class II-positive cells, was observed after LPS injection. CONCLUSIONS: A network of macrophages and MHC class II-positive cells in the iris and ciliary body may play an important role in immune surveillance. LPS injection induces a severe inflammation in the anterior segment of the eye, which may serve as a model for acute anterior uveitis in human.

Animals↗

Measuring geographic atrophy in advanced age-related macular degeneration.

PURPOSE: To present a method developed for measuring areas of geographic atrophy (GA) in advanced age-related macular degeneration, METHODS: A microfilm reader projected the 30 degrees fundus photograph of the macula. Retinal landmarks, atrophic areas, and spared areas within the atrophy were traced, without access to drawings of other years. The total atrophic area was calculated, as was the atrophy within a four-disc-area circle entered on the estimated foveal center. The configuration of the atrophy was documented. RESULTS: Avoidable sources of discrepancy included variability in peripapillary atrophy seen on the photograph, and variability seen in the extent of the field. Reproducibility studies found a median absolute difference of 0.19 Macular Photocoagulation Study disc areas (DA) in total atrophy between repeat drawings, with 75% of repeat drawings having a difference of less than 0.33 DA. For central atrophy measures, there was a median difference of 0.08 DA, with 75% of pairs having a difference of less than 0.18 DA. Features making the definition of borders of GA difficult include the presence of drusen and pigmentary alteration, a fundus in which choroidal vessels are easily visible, and variation in the appearance of GA within a single area of atrophy. CONCLUSIONS: This method provides a reliable means of measuring the size of atrophic areas in GA and will be useful for measuring longitudinal change. It may be difficult to determine whether central spared areas are present, and correlation with visual acuity and macular perimetry may be helpful.

Aged↗

MR-revealed myelination in the cerebral corticospinal tract as a marker for Pelizaeus-Merzbacher's disease with proteolipid protein gene duplication.

BACKGROUND AND PURPOSE: Pelizaeus-Merzbacher's disease (PMD) is caused by mutations in the proteolipid protein (PLP) gene. Recent studies have shown that an increased PLP dosage, resulting from total duplication of the PLP gene, invariably causes the classic form of PMD. The purpose of this study was to compare the MR findings of PMD attributable to PLP duplication with those of PMD arising from a missense mutation. METHODS: Seven patients with PMD, three with a PLP missense mutation in either exon 2 or 5 (patients 1-3), and four with PLP duplication (patient 4 having larger PLP duplication than patients 5-7) were clinically classified as having either the classic or connatal form of PMD. Cerebral MR images were obtained to analyze the presence of myelination and T1 and T2 shortening in the deep gray matter. Multiple MR studies were performed in six of the seven patients to analyze longitudinal changes. RESULTS: Four patients (patients 1-4) were classified as having connatal PMD, whereas the other three (patients 5-7) were classified as having classic PMD. Myelination in the cerebral corticospinal tract, optic radiation, and corpus callosum was observed in three cases of classic PMD with PLP duplication. In patient 4, myelination extended to the internal capsule, corona radiata, and centrum semiovale over a 3-year period. No myelination was observed in three PMD cases with a PLP point mutation. T2 shortening in the deep gray matter was recognized in all patients with PMD. CONCLUSION: The presence of myelination in the cerebral corticospinal tract with diffuse white matter hypomyelination on MR images could be a marker for PMD with PLP duplication. It is suggested that progression of myelination may be present in connatal PMD with large PLP duplication.

Adolescent↗

A birthweight nomogram for Africa, as a malaria-control indicator.

Low birthweight (LBW) attributable to malaria in pregnancy is a significant risk for millions in Africa. Infants born to primigravidae are at greatest risk and it is proposed that this excess risk can be used as a simple indicator of malaria transmission and exposure in pregnant women in Africa. Birthweight data from different regions in 11 malarious and three non-malarious African countries were investigated. A regression analysis of the excess risk of low birthweight in first pregnancies, compared with later ones, was completed and interpreted in relation to malaria-transmission intensities. The aim was to develop a simple birthweight chart (nomogram) as a tool for monitoring malaria transmission or malaria control in pregnancy. Low-birthweight risk in first pregnancies was associated with levels of malaria-transmission intensity amongst different African countries. The nomogram distinguished longitudinal changes in malaria exposure, related to season and changes in antimalarial-drug policy. Malaria is one of the most important causes of LBW in first pregnancies in Africa. As birthweight and parity are routinely recorded in many delivery centres across Africa, the nomogram provides a simple, available and inexpensive tool for monitoring malaria transmission and exposure in pregnant women and the effectiveness of malaria-control activities for this high-risk group.

Africa↗

Intra-observer repeatability and inter-observer agreement of the Smith method of measuring the anterior chamber depth.

The Smith (1979) method provides a means of estimating the anterior chamber depth without additional attachments to the slit lamp [Smith, R. J. H. (1979). A new method of estimating the depth of the anterior chamber. Br. J. Ophthalmol. 63, 215-220]. In this study, the 95% intra-observer limits of repeatability and the 95% inter-observer limits of agreement of this method have been determined. The intra-observer limits of repeatability were determined by plotting the difference vs the mean of the estimated anterior chamber depth obtained in two different sessions by each of two examiners, while the inter-observer limits of agreement are represented by a plot of the difference vs the mean estimated anterior chamber depth between the two examiners. For one examiner, the 95% intra-observer limits of repeatability was -0.36 to 0.58 mm, while for the other examiner the 95% intra-observer limits of repeatability was -0.25 to 0.37 mm. The 95% inter-observer limits of agreement were -0.31 to 0.23 mm and -0.41 to 0.25 mm for the first and second sessions respectively. The intra-observer limits of repeatability are comparable with those reported for A-scan ultrasonographic measures of the anterior chamber depth. These results imply that the Smith method can be used with a high degree of repeatability and agreement to clinically monitor longitudinal changes in anterior chamber depth.

Adult↗

Interpretation of quality-of-life outcomes: issues that affect magnitude and meaning.

When quality-of-life outcomes are used to evaluate treatment effectiveness, the importance of the treatment effect relative to other clinical factors is often difficult to assess. A major methodological issue addressed in this review is the interpretation of quality-of-life treatment effects. The problem is challenging for a number of reasons, including the subjective nature of the quality-of-life construct, the indirect way which it is assessed, the multiple sources of measurement error, the heterogeneity of the stochastic properties of longitudinal changes over the full range of the scale, the complex associations among multiple outcomes, and the lack of clearly directed therapeutic goals defined in terms of quality-of-life changes. The interpretation question can be addressed at 2 levels: measurement and inference. At the first level of measurement, it is necessary to establish the relevance of the quality-of-life metric across the distribution of changes by establishing meaningful category intervals that are important to the individual patient. The second level of inference involves an evaluation of the relative benefit of a quality-of-life improvement or the risk of a quality-of-life worsening for alternative treatments in populations in whom other issues, such as overall cost and available health resources, must also be considered. This report focuses on the quantitative issues that must be addressed in an interpretation of the treatment-related changes in quality-of-life outcomes. The conceptual framework of the problem is outlined, and problems that contribute to the interpretation dilemma are discussed.

Cost-Benefit Analysis↗

Influences of osteoclast deficiency on craniofacial growth in osteopetrotic (op/op) mice.

It is well known that the defect in bone resorption in osteopetrotic (op/op) mice brings about deformation of the cranium and failure of tooth eruption. However, the influences on longitudinal growth of the craniofacial skeleton have not been elucidated. This study was thus conducted to examine craniofacial morphology and longitudinal changes in the op/op mice by means of morphometric analysis with lateral cephalograms. Lateral cephalograms, taken every 10 days from 10- to 90-day-old mice, were analyzed on a personal computer for 11 measurement items. For the nasal bone region, the most prominent differences were found between the op/op and normal mice. The anterior cranial base and occipital bone height presented almost equivalent growth changes in both the op/op and normal mice. The size of mandible, meanwhile, was significantly smaller in the op/op mice than in the normal controls. The gonial angle was also significantly larger in the op/op mice than in the normal mice throughout the experimental period. Thus, substantial differences in craniofacial growth were demonstrated in various areas of the craniofacial complex, which are assumed essentially due to the lack of osteoclastic bone resorption during growing period. Since the difference became more prominent in the anatomic regions relevant to the masticatory functions, it would be a reasonable assumption that reduced masticatory function is also a key determinant for the less-developed craniofacial skeleton in the op/op mouse.

Animals↗

Differences in time course and visual requirements of ocular responses to lenses and diffusers.

PURPOSE: Myopia can be induced in chickens by having them wear either negative lenses (lens-compensation myopia [LCM]) or diffusers (form-deprivation myopia [FDM]), whereas positive lenses cause lens-compensation hyperopia (LCH). These three conditions were compared with respect to (i) their early time course and (ii) the effect of two manipulations of the lighting. METHODS: Longitudinal changes in ocular dimensions and refractive error were measured in chicks maintained under three different conditions: (i) wearing either -15 D lenses or diffusers in a normal light/dark cycle; (ii) wearing either +15 D lenses, -15 D lenses, or diffusers with brief periods of stroboscopic lights at the beginning and end of the dark period; (iii) wearing either +6 D lenses, -6 D lenses, or diffusers with the nights interrupted by brief periods of white light. In addition, scleral and choroidal proteoglycan synthesis was measured in eyes that wore positive lenses, negative lenses, or diffusers for 3 hours followed by different periods of darkness. RESULTS: (i) The time course of the changes in axial length over the first 72 hours was significantly faster in LCM than in FDM. Indeed, the diffusers did not begin to significantly affect the total length of the globe for 3 days, although the vitreous chamber had deepened after 9 hours, because the choroid thinned extremely rapidly (within 1 hour) with either diffusers or negative lenses. (ii) Scleral proteoglycan synthesis was higher in eyes with negative lenses than in those with diffusers at 11 hours, but the reverse was true at 27 hours. (iii) Brief periods of stroboscopic light attenuated FDM more than LCM. (iv) In contrast, interruption of the nights by brief periods of light attenuated LCM more than FDM. (v) Neither lighting manipulation affected LCH. (vi) Choroidal proteoglycan synthesis decreased similarly with 3 hours of wearing either diffusers or negative lenses. CONCLUSIONS: Although both negative lenses and diffusers cause similar increases in the rate of ocular elongation, the responses differ in time course and in the effect of manipulations of the daily lighting. The responses to positive lenses differ from both of these.

Animals↗

Application of yeast enolase as antigen for immunodiagnosis of malaria.

In 1998, we reported that Plasmodium falciparum (Pf) enolase was useful as the capture antigen for the immunodiagnosis of malaria. In the present study, we modified a fluorescence-ELISA for the diagnosis of malaria by applying yeast enolase or rabbit muscle enolase as antigen. Sera from 67 falciparum malaria patients and 15 vivax malaria patients were tested by the method. Positivity rates of the former was 82.1% against yeast enolase antigen and 90.5% against rabbit muscle enolase antigen, and those of latter was 93.3% against both enolase antigens. Mean antibody level (RFU values) of sera from falciparum and vivax malaria patients were significantly higher than those from healthy individuals. There was a significant correlation between anti-yeast and anti-rabbit muscle enolase antibody level (RFU values) in the group of falciparum subjects (r = 0.401, p<0.001). A significant correlation between RFU values against yeast enolase antigen and indirect fluorescent antibody titers against crude Pf antigen in the same subjects was recognized (r = 0.518, p<0.001). Longitudinal changes of RFU values against yeast enolase for the following 4 weeks after admission were also examined for sera from falciparum malaria patients. Patients with more severe malaria showed increasing RFU values as the clinical courses progressed. However, in the mild cases, each RFU value stayed unchanged during the course. We concluded that yeast and rabbit muscle enolase could be appropriately used as antigen for the immunodiagnosis of malaria.

Animals↗

Continuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.

To circumvent the potentially negative consequences of long-term exposure to unphysiologic acidic lactate-buffered peritoneal dialysis fluids (PDF), neutral pH solutions buffered with bicarbonate/lactate have recently been introduced in phase 2 and 3 clinical trials. This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF. Before the study, during the run in period of a phase 3 clinical trial, all patients had been taking LPD for at least the previous 18 wk. At the beginning of the study (day 0), both constitutive and serum-treated zymosan (STZ) stimulated tumor necrosis factor alpha (TNF-alpha) synthesis were assessed in PMØ isolated from 12-h dwell effluent (with 1.36% glucose) in all patients. The patients were subsequently randomized to either continuous TBL or LPD therapy and PMØ function was assessed after further 3- and 6-mo periods in all patients. At all time points measured STZ induced a dose-dependent increase in PMØ TNF-alpha secretion (P = 0.043 versus control for doses greater than 100 microg/ml). In patients continuously dialyzed with LPD, constitutive PMØ TNF-alpha synthesis levels (mean +/- SEM, pg/10(6) PMØ per18 h, n = 5 patients) were 154 +/- 65, 261 +/- 60, and 101 +/- 99 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1340 +/- 519, 1046 +/- 586, and 758 +/- 250 at 0, 3, and 6 mo, respectively. In patients dialyzed with TBL, constitutive PMØ TNF-alpha synthesis levels (pg/10(6) PMØ per 18 h, n = 5 patients) were 300 +/- 136, 106 +/- 35, and 213 +/- 62 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 microg/ml) levels were 1969 +/- 751, 1541 +/- 330, and 2670 +/- 671 at 0, 3, and 6 mo, respectively. At 6 mo, STZ-stimulated PMØ TNF-alpha synthesis was significantly higher in patients treated with TBL compared with those treated with LPD (P = 0.0035). These data suggest that in patients continuously dialyzed with a neutral pH solution, there is a long-term improvement in PMØ function compared with patients on conventional therapy. Better PMØ function suggests improved host defense status and may affect the peritoneum's susceptibility to infection and potentially reduce the negative consequences of repeated intraperitoneal inflammation on long-term membrane function.

Aged↗

Longitudinal neuropsychological effects of n-hexane exposure: neurotoxic effects versus depression.

Human exposure to n-hexane (a hexacarbon solvent) is relatively frequent as it is used in many industries as a solvent, a thinner, and a cleaning agent. This report examines a case of peak n-hexane exposure, involving known exposure to high levels over a relatively brief period of time. Peak exposure is a risk factor for persisting neuropsychological impairment. However, cognitive deficits and depression have not been measured in studies of n-hexane, and only peripheral neuropathy, often reversible, is thought to be the neurological risk. This case demonstrates the longitudinal patterns of neuropsychological functions and emotion, and represents the early and late developing effects of n-hexane exposure that parallel the longitudinal change reported in groups of workers with solvent exposure.

Journal Article↗

Epidemiology of obstructive sleep apnea syndrome.

The association of obstructive sleep apnea (OSA) syndrome with obesity, hypertension and cardiovascular disease has highlighted the broad public health importance of this condition. OSA affects at least 9% to 15% of middle-aged adults. Both epidemiological and sleep clinic-based studies indicate that OSA is more common in men than in women. However, the ratio of men to women with OSA in clinical studies appears to be considerably higher than in the community: up to 8:1 versus 2 to 3:1. Cross sectional studies on OSA prevalence showed effects of age, independently from the unfortunate propensity for a rising body mass index (BMI) with age: an approximate doubling of apnea-hypopnea index (AHI) every 10 years has been reported. A recent prospective study with 4-year follow-up showed that a 10% weight gain predicted a 32% increase in AHI, whereas a 10% loss in weight predicted a 26% decrease in AHI. Another 5-year prospective study found that longitudinal change in AHI varies nonuniformly with age, sex and weight: older heavier may experience the highest rate of AHI increase over time and, thus, may benefit most from prospective monitoring.

Age Factors↗

Comparison of multifidus muscle atrophy and trunk extension muscle strength: percutaneous versus open pedicle screw fixation.

STUDY DESIGN: This study was conducted by retrospective case selection and prospective observation of longitudinal changes of the multifidus muscle cross-sectional area and of trunk extension muscle strength in percutaneous and open pedicle screw fixations. OBJECTIVES: To compare postoperative multifidus muscle atrophy and trunk muscle performance of percutaneous pedicle screw fixation against those of open pedicle screw fixation. SUMMARY OF BACKGROUND DATA: Recent attempts to combine percutaneous pedicle screw fixation with minimally invasive fusion techniques are based on an anecdotal presupposition that percutaneous pedicle screw fixation is superior to its open counterpart. However, the benefits of percutaneous pedicle screw fixation are currently poorly defined. METHODS: Nineteen enrolled patients were divided as follows: 11 in the open pedicle screw fixation group (OPF group) and eight in the percutaneous pedicle screw fixation group (PPF group). The preoperative and postoperative cross-sectional area and T2-weighted signal intensity of multifidus muscle were measured by MRI, and trunk extension muscle strength was measured. In addition, various clinical variables were compared between two groups. RESULTS: There was significant decrease in the cross-sectional area of multifidus muscle in the OPF group. In contrast, the results in the PPF group showed no statistical difference between preoperative results and that of the follow-up MRI. Although percutaneous pedicle screw fixation had positive effects on postoperative trunk muscle performance, clinical outcomes were not significantly different in areas of pain score, JOA score, and patient's opinion regarding the outcome of the surgery. However, percutaneous pedicle screw fixation caused less blood loss, and the proportion of patients who did not need postoperative oral analgesics was greater in the PPF group. CONCLUSIONS: Percutaneous pedicle screw fixation caused less paraspinal muscle damage than open pediclescrew fixation and had positive effects on postoperative trunk muscle performance.

Aged↗

Predictor of cognitive deterioration in elderly subjects by auditory-evoked magnetic signal using magnetoencephalography.

Recent development of auditory-evoked magnetoencephalography (A-MEG) made it possible to measure interhemispheric neural conduction time (INCT) of auditory impulses. We estimated INCT with A-MEG and cognitive function with mini-mental state examination (MMSE) in 85 elderly patients with chronic dizziness (CD) and found that INCT was negatively correlated with MMSE scores (p<0.001). In 11 of 85 patients whose MMSE scores were within the normal range, A-MEG and MMSE were repeated for the subsequent 4 years to find longitudinal changes in INCT and cognitive function. The 11 patients were divided into two groups according to the baseline INCT values, such as Group A with normal INCT (n=7) and Group B with abnormally prolonged INCT (n=4). In Group A, INCT and MMSE scores remained within the normal range throughout the 4-year period. In Group B, INCT showed the tendency towards progressive prolongation during the follow-up period, and MMSE scores decreased to abnormally low levels at the third or fourth follow-up year in all the patients. The present results suggest that rapid neural interaction of both cerebral hemispheres is needed to maintain normal cognitive function. Abnormal INCT prolongation in elderly subjects suggests subclinical cortical network dysfunction and may predict the future development of cognitive deterioration.

Acoustic Stimulation↗

Punctate palmoplantar keratoderma (Buschke-Fischer-Brauer disease) with psoriasis: a rare association showing excellent response to acitretin.

Hereditary punctate palmoplantar keratoderma (Buschke-Fischer-Brauer disease) is a rare disorder of keratinization. We describe here a 49-year-old male patient of this condition with many unusual features such as late onset of the disease in the fourth decade and nail changes (longitudinal pigmented striations, curved nails and pits in the fingernails; and nail thickening, subungual hyperkeratosis and yellowish discoloration in toenails). The patient developed histopathologically proven skin lesions typical of psoriasis 7 years after appearance of the keratoderma. This association has not been reported earlier. The patient's skin lesions cleared completely with acitretin therapy within 3 months.

Acitretin↗

Internal quality control of semen analysis.

OBJECTIVE: To test a scheme for quality control of semen analysis. DESIGN: The reproducibility of assessment of sperm concentration, motility, and morphology was obtained for the same sample measured by different technicians (between or intertechnician variation) and for different samples assessed by each technician with time (within or intratechnician variation). SETTING: Andrology Laboratory. PATIENTS: Semen samples were analyzed from all patients attending the clinic. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Within technician and between technician coefficients of variation for concentration, motility, and morphology. RESULTS: When 100 sperm were routinely assessed, both intratechnician variation, as assessed from the precision of duplicate measurements, and intertechnician variation revealed hyperbolic curves with increasing variation at low percentages (less than 20) of motile or morphological forms. When these low values were excluded, mean intratechnician variations were 5.0%, 8.4%, and 2.8% for concentration, motility, and morphology, respectively, and mean intertechnician variations were, respectively, 6.1%, 5.6%, and 5.6%. Similar mean intertechnician variation for morphology was obtained for repeated assessment of prestained (7.3%) or presmeared (5.9%) slides. The use of cryopreserved semen to monitor longitudinal changes in the technicians' assessments revealed variations of 8.1% to 12% in concentration and 9.7% to 14% in motility. Computing the monthly means for sperm concentration, motility, and morphology over a 4.5-year period revealed a marked reduction in percentage of normal morphological forms, unrelated to the sperm count or mean age of the men attending the clinic. This was shown to be a result of a shift in the assessment by technicians. CONCLUSIONS: Quality control is necessary and possible in an andrology clinic.

Cryopreservation↗

Current status of general practice research in Australia. Analysis of a national database.

OBJECTIVE: To describe the current status of general practice research activity in Australia. DESIGN: A descriptive survey of research projects included in a national research database, established by the Royal Australian College of General Practitioners. The study instrument was a mailed questionnaire. SETTING AND PARTICIPANTS: Research projects involving or directly related to general practice that had commenced in Australia since 1 January 1989. Responses were specifically sought from all universities, the Family Medicine Programme and the Royal Australian College of General Practitioners. RESULTS: Two hundred and thirty-seven projects from 130 different principal investigators, one-third of whom were not medical practitioners, were analysed. Over 85% of research took place in association with a recognised tertiary institution. Over half of the projects were descriptive only; the most common areas were medical education, prevention and screening and health services research. Of the 69 projects completed prior to 1991, 49 had been submitted for publication and 26 had been accepted. CONCLUSIONS: The amount of general practice research undertaken in Australia is still small in relation to the size of the workforce, and most are descriptive studies. This national database will enable longitudinal changes in such patterns to be effectively monitored.

Australia↗