Interventions for enhancing return to work in individuals with a common mental illness: systematic review and meta-analysis of randomized controlled trials.

Common mental disorders (CMDs) are highly prevalent in the working population, and are associated with long-term sickness absence and disability. Workers on sick leave with CMDs would benefit from interventions that enable them to successfully return to work (RTW). However, the effectiveness of RTW interventions for workers with a CMD is not well studied. The objective of this review is to assess the effectiveness of existing workplace and clinical interventions that were aimed at enhancing RTW. A systematic review of studies of interventions for improving RTW in workers with a CMD was conducted. The main outcomes were proportion of RTW and sick-leave duration until RTW. Randomized controlled trials (RCTs) were identified from Medline/PubMed, PsycINFO, EMBASE, SocINDEX, and Human resource and management databases from January 1995 to 2016. Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently homogeneous in different comparison groups and assessed the overall quality of the evidence. We reviewed 2347 abstracts from which 136 full-text articles were reviewed and 16 RCTs were included in the analysis. Combined results from these studies suggested that the available interventions did not lead to improved RTW rates over the control group [pooled risk ratio 1.05, 95% confidence interval (CI) 0.97-1.12], but reduced the number of sick-leave days in the intervention group compared to the control group, with a mean difference of -13.38 days (95% CI -24.07 to -2.69).

Expression in Escherichia coli of open reading frame gene segments of HTLV-III.

Human T-cell lymphotropic virus type III (HTLV-III), the causative agent of the acquired immune deficiency syndrome (AIDS), was recently isolated and its genomic structure analyzed by DNA cloning methods. In the studies reported here a combined cloning and expression system was used to identify HTLV-III encoded peptides that react immunologically with antibodies in sera from AIDS patients. Cloned HTLV-III DNA was sheared into approximately 500-base-pair fragments and inserted into an "open reading frame" expression vector, pMR100. The inserted DNA was expressed in Escherichia coli transformants as a polypeptide fused to the lambda CI protein at its amino terminus and to beta-galactosidase at its carboxyl terminus. Sera from AIDS patients containing antibodies to HTLV-III were then used to screen for immunoreactive fusion proteins. Twenty clones, each specifying a fusion protein strongly reactive with AIDS serum, were identified. DNA sequence analysis indicated that the HTLV-III fragments were derived from the open reading frame DNA segments corresponding to the gag and pol gene coding regions and also the large open reading frame region (env-lor) located near the 3' end of the viral genome.

New cutpoints to identify increased HER2 copy number: analysis of a large, population-based cohort with long-term follow-up.

BACKGROUND: HER2 gene amplification and/or protein overexpression in breast cancer is associated with a poor prognosis and predicts response to anti-HER2 therapy. We examine the natural history of breast cancers in relationship to increased HER2 copy numbers in a large population-based study. PATIENTS AND METHODS: HER2 status was measured by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in approximately 1,400 breast cancer cases with greater than 15 years of follow-up. Protein expression was evaluated with two different commercially-available antibodies. RESULTS: We looked for subgroups of breast cancer with different clinical outcomes, based on HER2 FISH amplification ratio. The current HER2 ratio cut point for classifying HER2 positive and negative cases is 2.2. However, we found an increased risk of disease-specific death associated with FISH ratios of >1.5. An 'intermediate' group of cases with HER2 ratios between 1.5 and 2.2 was found to have a significantly better outcome than the conventional 'amplified' group (HER2 ratio >2.2) but a significantly worse outcome than groups with FISH ratios less than 1.5. CONCLUSION: Breast cancers with increased HER2 copy numbers (low level HER2 amplification), below the currently accepted positive threshold ratio of 2.2, showed a distinct, intermediate outcome when compared to HER2 unamplified tumors and tumors with HER2 ratios greater than 2.2. These findings suggest that a new cut point to determine HER2 positivity, at a ratio of 1.5 (well below the current recommended cut point of 2.2), should be evaluated.

Biomarkers of oxidative stress in schizophrenic and control subjects.

Increasing evidence indicates that oxidative injury exists in schizophrenia. Although it may not be the main cause, oxidative damage has been suggested to contribute to the pathophysiology and may account for deteriorating course and poor outcome in schizophrenia. A human study was undertaken, therefore, to investigate possible differences in biomarkers of DNA, lipid and protein oxidation in schizophrenic (n=16) and control subjects (n=17). Plasma vitamin C levels were also compared in both groups. Cellular DNA damage and plasma protein carbonyl levels were increased in the schizophrenic group compared to control subjects but not significantly. However, DNA damage in lymphocytes from the male schizophrenic group was significantly higher than the female group. Biomarkers of lipid peroxidation and plasma vitamin C levels also revealed no significant difference between the two groups under investigation, although a significant elevation in plasma vitamin C was observed in the female control group when compared to the male groups.

Influence of measurement error on assessment of response to anticancer chemotherapy: proposal for new criteria of tumor response.

The decision to use a given type of chemotherapy to treat cancer patients is often based on the prior demonstration that a proportion of similar patients has "responded" in a clinical trial. Most responses are recorded as a partial shrinkage of tumor, defined usually as a greater than 50% shrinkage of the sum of cross-sectional areas of index lesions for at least one month. The errors in categorization of response have been estimated by comparing measurements of several physicians on real or simulated malignant lesions. False categorization of partial response based on a comparison of two measurements of the same lesion was 1.3% and 12.6% for large and small simulated nodules, respectively, 13.1% for malignant neck nodes, and 0.8% for metastatic lung nodules. Partial response for hepatic lesions has been defined by a 50% or 30% decrease in liver span below the costal margin; these definitions led to a false categorization of partial response of 8.5% and 18.4%, respectively. Larger errors are evident when using the current definition of disease progression that requires only a 25% increase in area. False categorization of response is increased by comparing any of serial measurements with the initial lesions, as is usually done clinically. Many published trials have used criteria for response that are subject to large errors; an uncritical interpretation of their results may lead to inappropriate treatment of patients. Based on the results, new criteria for evaluating tumor response are proposed.

Colony growth and self renewal of plasma cell precursors in multiple myeloma.

Culture conditions that support the growth of multi-and single-lineage hemopoietic colonies are also able to give rise to large myeloma colonies from bone marrow and peripheral blood samples of some patients with multiple myeloma. The culture system was used to determine the frequency of hemopoietic precursors and clonogenic myeloma progenitors in 71 patients with multiple myeloma studied in various clinical phases of the disease. The frequency of normal hemopoietic precursors in patients with benign monoclonal gammopathy and smoldering myeloma were indistinguishable from normal controls. Myeloma colonies were not observed in these subgroups. In contrast, patients with active disease showed significantly reduced hemopoietic colony formation, even before the initiation of therapy. A further reduction was demonstrated for patients with acute phase disease. A correlation between the frequency of hemopoietic colonies and the concentration of plasma cells in the plated sample was not observed. Large myeloma colonies with recloning potential were identified in cultures of specimens derived from 14 of the studied patients. These colonies were most frequently (ten cases) obtained from patients who had entered the acute phase of the disease. These patients manifested marrow failure (pancytopenia) and their marrow had a limited capacity to generate normal hemopoietic colonies. Three of the patients that formed myeloma colonies were studied in chronic phase following chemotherapy and one patient was examined at diagnosis. The myeloma colonies were composed exclusively of cells characterized by the same M protein as the patient. Some of the cells within the colonies retained their ability to self renew extensively, as demonstrated by serial recloning studies. Colonies derived from six of the patients are now propagated in semisolid and liquid medium for as many as nine to 34 generations. Patients that form myeloma colonies under these culture conditions represent a high-risk group with significantly shorter survival than patients not able to give rise to myeloma colonies. A Cox proportional hazards model was fitted to the data to determine the prognostic role of myeloma colony growth in culture after accounting for the influence of other well established risk factors, such as concentration of plasma cells and disease status. The analysis indicated that myeloma colony growth in culture serves as a strong and independent predictive indicator of poor clinical prognosis.

Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients.

This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.

Obesity in black adolescent girls: a controlled clinical trial of treatment by diet, behavior modification, and parental support.

Recent findings indicate that nearly 50% of black American women are obese and that adolescence is a critical period for the development of their obesity. This study investigated the efficacy of a behavioral weight control program in 36 black female adolescents with a mean age of 14.0 years, weight of 95.0 kg, and height of 163.2 cm. All subjects participated in the same 16-week program but had different levels of parent participation: (1) child alone with no parent participation; (2) mother and child treated in the same session; and (3) mother and child treated in separate but concurrent session. At the end of the 16-week program, children in the three conditions lost 1.6, 3.7, and 3.1 kg, respectively. Differences among conditions were not statistically significant; however, a secondary analysis revealed that the greater the number of sessions attended by mothers, the greater their daughters' weight losses. Weight reduction was associated with significant improvements in body composition, serum total cholesterol concentrations, and psychological status. Results are discussed in terms of the need to improve the maintenance of weight loss in adolescents and to explore possible differences between black and white females in their preferred body types.

A novel HLA-A*8001 allele identified in an African-American population.

HLA polymorphism varies among different racial origins. Certain antigens are restricted to a particular ethnic group, suggesting that genetic events might have generated further unique polymorphism following racial diversification. In this study, we have identified and characterized a novel HLA-A allele, officially designated A*8001. The class I molecule, HLA-AXBG, encoded by this allele could not be defined by commonly available HLA antisera. We have identified two alloantisera that appear to be monospecific for this new antigen. The observed frequency of AXBG antigen specificity is 2% in African Americans among the total of 254 tested, but it has not been found in 305 Caucasians tested. IEF and cDNA sequencing analyses on multiple individuals revealed that AXBG antigen defined by the two antisera are encoded by an identical HLA-A*8001 allele and it has a number of unique amino acid residues that have not been observed among other HLA-A alleles but are known to occur in certain human nonclassic class I genes and nonhuman primate class I genes. The ability to identify the new HLA-AXBG antigen will improve the precision of HLA-A typing in black populations and enable us to match a patient with a donor for this otherwise undefined antigen in transplantation.

Regression and recursive partition strategies in the analysis of medical survival data.

Regression and clustering methods have both been used to explore the effects of explanatory variables on survival times for patients with cancer or other chronic diseases. This paper discusses effective and computationally feasible approaches for this task in situations where there are fairly large and complex data sets; the techniques stressed are all-subsets regression and a kind of recursive partition clustering. We compare the two approaches in a rather general way, in part by examining some survival data for patients with ovarian carcinoma, and conclude that both have strong points to recommend them.

Habituation in goldfish (Carassius auratus) is impaired by increased interstimulus interval, interval variability, and telencephalic ablation.

Goldfish (Carassius auratus) were fitted with electrodes and buccal catheters for monitoring electrocardiograms and ventilations, respectively. A 2-s "light-on" stimulus was repeatedly presented to groups of fish at fixed interstimulus intervals (ISIs) of 1 or 2 min or at variable ISIs with a mean duration of 1 or 2 min. Normal fish, fish with telencephalic ablation, and fish with sham operations were compared for responsiveness and habituation to repeatedly presented stimuli. The longer the ISI, the greater the number of stimuli that were required for habituation. Increased ISI variability also decreased the rate of habituation. Furthermore, fish with telencephalic ablation had significantly slower habituation rates with both fixed and variable ISI schedules.

Spatial pattern of pulmonary blood flow distribution is stable over days.

Despite the heterogeneous distribution of regional pulmonary perfusion over space, local perfusion remains stable over short time periods (20-100 min). The purpose of this study was to determine whether the spatial distribution of pulmonary perfusion remains stable over longer time periods (1-5 days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of different colors were injected into a limb vein over 30 s on each day. After the last microsphere injection, the dogs were killed, and lungs were flushed free of blood, excised, dried at total lung capacity, and diced into approximately 2-cm3 pieces (n = 1,296-1,487 per dog). Relative blood flow to each piece on each day was determined by extracting the fluorescent dyes and determining the concentrations of each color. We established that blood flow is spatially heterogeneous with a coefficient of variation of 29.5 +/- 2%. Blood flow to each piece is highly correlated with flow to the same piece on all days (r = 0.930 +/- 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 +/- 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variation is significantly less than previously reported in a study in which anesthetized and mechanically ventilated dogs were used. We conclude that spatial distribution of pulmonary blood flow remains stable over days and we speculate that in the normal awake dog regional perfusion is determined primarily by a fixed structure such as the geometry of the pulmonary vascular tree rather than by local vasoactive regulators. Anesthesia and/or mechanical ventilation may increase the temporal variability in regional perfusion.

Fractal nature of regional ventilation distribution.

High-resolution measurements of pulmonary perfusion reveal substantial spatial heterogeneity that is fractally distributed. This observation led to the hypothesis that the vascular tree is the principal determinant of regional blood flow. Recent studies using aerosol deposition show similar ventilation heterogeneity that is closely correlated with perfusion. We hypothesize that ventilation has fractal characteristics similar to blood flow. We measured regional ventilation and perfusion with aerosolized and injected fluorescent microspheres in six anesthetized, mechanically ventilated pigs in both prone and supine postures. Adjacent regions were clustered into progressively larger groups. Coefficients of variation were calculated for each cluster size to determine fractal dimensions. At the smallest size lung piece, local ventilation and perfusion are highly correlated, with no significant difference between ventilation and perfusion heterogeneity. On average, the fractal dimension of ventilation is 1.16 in the prone posture and 1. 09 in the supine posture. Ventilation has fractal properties similar to perfusion. Efficient gas exchange is preserved, despite ventilation and perfusion heterogeneity, through close correlation. One potential explanation is the similar geometry of bronchial and vascular structures.

Correlation between ventilation and perfusion determines VA/Q heterogeneity in endotoxemia.

Endotoxin increases ventilation-to-perfusion ratio (VA/Q) heterogeneity in the lung, but the precise changes in alveolar ventilation (VA) and perfusion that lead to VA/Q heterogeneity are unknown. The purpose of this study was to determine how endotoxin affects the distributions of ventilation and perfusion and the impact of these changes on VA/Q heterogeneity. Seven anesthetized, mechanically ventilated juvenile pigs were given E. coli endotoxin intravenously, and regional ventilation and perfusion were measured simultaneously by using aerosolized and injected fluorescent microspheres. Endotoxemia significantly decreased the correlation between regional ventilation and perfusion, increased perfusion heterogeneity, and redistributed perfusion between lung regions. In contrast, ventilation heterogeneity did not change, and redistribution of ventilation was modest. The decrease in correlation between regional ventilation and perfusion was responsible for significantly more VA/Q heterogeneity than were changes in ventilation or perfusion heterogeneity. We conclude that VA/Q heterogeneity increases during endotoxemia primarily as a result of the decrease in correlation between regional ventilation and perfusion, which is in turn determined primarily by changes in perfusion.

Temporal heterogeneity of regional pulmonary perfusion is spatially clustered.

This study investigates temporal changes in regional pulmonary perfusion. Five dogs were studied with five or six different radiolabeled microspheres being injected via a central vein over 30 s every 20 min. The lungs of each animal were cubed into 1.9 cm3 pieces with spatial coordinates noted for each piece. Within individual pieces, the coefficient of variation of regional perfusion over time was 17.2 +/- 6.8% (SD) and across dogs accounted for 7.26 +/- 5.7% of total perfusion heterogeneity. Temporal variability or "twinkling" was not random. When lung pieces with similar temporal flow patterns were grouped together (regardless of spatial location), groups were more tightly clustered in space than expected by chance. Statistical clustering methods revealed regulation of blood flow on a large scale (lobar arteries), and fractal analyses suggested regulation existed on a smaller scale (arterioles). We conclude that regional pulmonary perfusion is heterogeneous over time in a nonrandom pattern and that pieces clustered by temporal patterns of perfusion are neighbors in the spatial domain.

Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation.

To explore mechanisms of hypoxemia after acute pulmonary embolism, we measured regional pulmonary blood flow and alveolar ventilation before and after embolization with 780-micrometers beads in five anesthetized, mechanically ventilated pigs. Regional ventilation and perfusion were determined in approximately 2.0-cm3 lung volumes by using 1-micrometers-diameter aerosolized and 15-micrometers-diameter injected fluorescent microspheres. Hypoxemia after embolization resulted from increased perfusion to regions with low ventilation-to-perfusion ratios. Embolization caused an increase in perfusion heterogeneity and a fall in the correlation between ventilation and perfusion. Correlation between regional ventilation pre- and postembolization was greater than correlation between regional perfusion pre- and postembolization. The majority of regional ventilation-to-perfusion ratio heterogeneity was attributable to changes in regional perfusion. Regional perfusion redistribution without compensatory changes in regional ventilation is responsible for hypoxemia after pulmonary vascular embolization in pigs.

Exercise alters fractal dimension and spatial correlation of pulmonary blood flow in the horse.

We determined the changes in fractal dimensions and spatial correlations of regional pulmonary blood flow with increasing exercise in race horses (n = 4) by using 15-microm fluorescent microspheres. Fluorescence was measured to quantitate regional blood to 1.3-cm(3) samples (n = 1,621-2,503). Perfusion distributions were characterized with fractal dimensions (a measure of spatial variability) and spatial correlations. On average, the fractal dimension decreased with exercise (trot 1.216 to gallop 1.173; P < 0. 05) despite a variable fractal dimension at rest. Spatial correlation of flow to neighboring pieces increased with exercise (trot 0.57 +/- 0.074 to gallop 0.73 +/- 0.051) and was inversely correlated with fractal dimension, indicating better spatial correlation as blood flow distribution becomes more uniform. This is the first study to document a change in fractal dimension as a result of increasing pulmonary blood flow. Spatial differences in response to vasoregulatory mediators may play a role in this phenomenon.

Mechanisms of improvement in pulmonary gas exchange during isovolemic hemodilution.

Severe anemia is associated with remarkable stability of pulmonary gas exchange (S. Deem, M. K. Alberts, M. J. Bishop, A. Bidani, and E. R. Swenson. J. Appl. Physiol. 83: 240-246, 1997), although the factors that contribute to this stability have not been studied in detail. In the present study, 10 Flemish Giant rabbits were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Serial hemodilution was performed in five rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; five rabbits were followed over a comparable time. Ventilation-perfusion (VA/Q) relationships were studied by using the multiple inert-gas-elimination technique, and pulmonary blood flow distribution was assessed by using fluorescent microspheres. Expired nitric oxide (NO) was measured by chemiluminescence. Hemodilution resulted in a linear fall in hematocrit over time, from 30 +/- 1.6 to 11 +/- 1%. Anemia was associated with an increase in arterial PO(2) in comparison with controls (P < 0.01 between groups). The improvement in O(2) exchange was associated with reduced VA/Q heterogeneity, a reduction in the fractal dimension of pulmonary blood flow (P = 0.04), and a relative increase in the spatial correlation of pulmonary blood flow (P = 0. 04). Expired NO increased with anemia, whereas it remained stable in control animals (P < 0.0001 between groups). Anemia results in improved gas exchange in the normal lung as a result of an improvement in overall VA/Q matching. In turn, this may be a result of favorable changes in pulmonary blood flow distribution, as assessed by the fractal dimension and spatial correlation of blood flow and as a result of increased NO availability.

Restraint, dieting, and the continuum model of bulimia nervosa.

The authors evaluated the continuity model of bulimia nervosa, which suggests that bulimia results from extreme weight concern and dieting practices. Individuals with bulimia, current dieters, restrained nondieters, and unrestrained nondieters were compared on measures of general psychopathology, eating-disorder-specific psychopathology, and overeating. Multiple methods, including questionnaires, clinical interviews, and food records, were used to collect data. The continuity and discontinuity models were tested with trend and regression analyses. The results of most analyses were consistent with the continuity perspective. However, binge eating behaviour exhibited a clear nonlinear trend, which occurred because binge eating was common in bulimic individuals but virtually non-existent in the other 3 groups. Current dieters scored higher than restrained nondieters on restraint/ weight concern, but not on psychopathology or binge eating. Overall, the results suggest that "normal" dieting is associated with psychological, but not consummatory, symptoms of bulimia.

Who does the public think should perform health care tasks?

The dietitian was identified as the most appropriate provider of such key nutrition services as nutrition assessment, determination of caloric requirements, provision of diet counseling, and prescription of diets. Several tasks fundamental to nutrition services were not viewed as highly suitable tasks for the dietitian, e.g., plan for care at home, monitor client progress, and check laboratory values. Activities that constitute key nutrition services need to be accentuated to clarify the numerous skills and extensive knowledge that dietitians possess. In the health care system of today, the dietetic profession must be associated with a wider range of health-related tasks than the traditional triad of diet, food, and hospital. Public relations and marketing strategies should focus on activities that provide the public with a clearer understanding of how the dietetic profession contributes to patient/client care.