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Although clinical intuitions influence psychotherapeutic practice and are a rich source of novel hypotheses for research, many remain to be empirically tested. This study evaluates whether clinicians' beliefs about barriers to progress in cognitive-behavioral therapy (CBT) for panic disorder are supported by data. Data from a randomized-controlled trial comparing CBT to panic-focused psychodynamic psychotherapy (PFPP) for adults with primary panic disorder (N = 161) were used to evaluate 15 factors endorsed by clinicians as impediments to CBT in a recent survey. Panic severity was assessed before, during (at Weeks 1, 5, and 9), and at termination of treatment (Week 12) using the Panic Disorder Severity Scale. Hierarchical linear modeling revealed that none of the perceived barriers were predictive of poor outcome. Contrary to clinicians' intuitions, dissociation during panic attacks was associated with greater symptomatic improvement in both treatment arms (β = -0.69, p < .05), above the effect of established predictors. Moderation analyses revealed that when patients had PTSD diagnosed with the Anxiety Disorders Interview Schedule (β = 1.71, p < .05) or less severe panic disorder (β = 0.45, p = .04), they changed more rapidly in CBT than in PFPP. Overall, clinician agreement was inversely related to the strength of a predictor (r = -.24, p = .39). Although clinical intuitions can be useful as clinical and empirical signals, such beliefs should be critically examined before informing practice. Dialogue between academics and clinicians might be enhanced through research that incorporates input from front-line practitioners., (Copyright © 2021. Published by Elsevier Ltd.)

Psychodynamic therapy (PDT) is an umbrella concept for treatments that operate on an interpretive-supportive continuum and is frequently used in clinical practice. The use of any form of psychotherapy should be supported by sufficient evidence. Efficacy research has been neglected in PDT for a long time. In this review, we describe methodological requirements for proofs of efficacy and summarise the evidence for use of PDT to treat mental health disorders. After specifying the requirements for superiority, non-inferiority, and equivalence trials, we did a systematic search using the following criteria: randomised controlled trial of PDT; use of treatment manuals or manual-like guidelines; use of reliable and valid measures for diagnosis and outcome; adults treated for specific mental problems. We identified 64 randomised controlled trials that provide evidence for the efficacy of PDT in common mental health disorders. Studies sufficiently powered to test for equivalence to established treatments did not find substantial differences in efficacy. These results were corroborated by several meta-analyses that suggest PDT is as efficacious as treatments established in efficacy. More randomised controlled trials are needed for some mental health disorders such as obsessive-compulsive disorder and post-traumatic stress disorder. Furthermore, more adequately powered equivalence trials are needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims of this study were (a) to summarize the psychometric literature on the Mobility Inventory for Agoraphobia (MIA), (b) to examine the convergent and discriminant validity of the MIA's Avoidance Alone and Avoidance Accompanied rating scales relative to clinical severity ratings of anxiety disorders from the Anxiety Disorders Interview Schedule (ADIS), and (c) to establish a cutoff score indicative of interviewers' diagnosis of agoraphobia for the Avoidance Alone scale. A meta-analytic synthesis of 10 published studies yielded positive evidence for internal consistency and convergent and discriminant validity of the scales. Participants in the present study were 129 people with a diagnosis of panic disorder. Internal consistency was excellent for this sample, α=.95 for AAC and .96 for AAL. When the MIA scales were correlated with interviewer ratings, evidence for convergent and discriminant validity for AAL was strong (convergent r with agoraphobia severity ratings=.63 vs. discriminant rs of .10-.29 for other anxiety disorders) and more modest but still positive for AAC (.54 vs. .01-.37). Receiver operating curve analysis indicated that the optimal operating point for AAL as an indicator of ADIS agoraphobia diagnosis was 1.61, which yielded sensitivity of .87 and specificity of .73., (Copyright © 2011. Published by Elsevier Ltd.)

Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL.

Objective: To examine the effect of perceived health status on three components of patient satisfaction., Methods: The Household Component of the 1999 Medical Expenditure Panel Survey for people 35-64 years of age was used to examine the effect of perceived health status on patient satisfaction measured in terms of access to care, provider quality and quality of care. Descriptive statistics and multivariate regression were used to describe the subjects and to examine the relationship between patient satisfaction and perceived health status controlling for patient demographic factors, health factors and provider characteristics. All analyses used STATA 8.0 which is designed to analyze weighted data., Results: A total of 4,417 patients (71% women) met the inclusion criteria for the study. Patients who rated their health excellent or good scored higher on the three dimensions of patient satisfaction. Higher scores on one or more components of patient satisfaction were associated with being older, married, better educated and having higher income, health insurance and good mental health. Seeing the health-care provider for an old problem resulted in lower levels of patient satisfaction. Provider characteristics significantly related to patient satisfaction were listening to the patient, being a specialist, seeing patients in an office setting and being located in the South., Conclusions: This study has shown that patient satisfaction is influenced by a person's self-perceived health status and other personal characteristics that are external to the delivery of health care. These findings suggest that patient satisfaction data should be used judiciously because a significant portion of the variation may be attributed to factors endogenous to the patient and therefore are not amenable to provider intervention.

The goals of this study were twofold: to examine the psychometric properties of the Multidimensional Anxiety Scale for Children (MASC) in a clinical sample of 193 children and adolescents who had received a diagnosis of major depressive or anxiety disorder, and to discriminate between these two groups of patients. Participants had volunteered in randomized psychopharmacological clinical trials. The MASC four-factor structure was confirmed and its subscales were found to be reliable. The MASC correlated well with other self-report measures of anxiety, and less so with measures of depressive symptoms. The MASC subscales and two MASC items as well as age differentiated between anxious and depressed pediatric patients. If these results are replicated in an independent study, those items could be used by clinicians to discriminate between these two disorders. The MASC is a clinically useful measure to discriminate between anxious and depressed pediatric patients. Limitations due to the highly selective sample are noted.

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by phosphatidylinositol glycan-class A (PIG-A) mutations in hematopoietic stem cells (HSCs). PIG-A mutations have been found in granulocytes from most healthy individuals, suggesting that these spontaneous PIG-A mutations are important in the pathogenesis of PNH. It remains unclear if these PIG-A mutations have relevance to those found in PNH. We isolated CD34+ progenitors from 4 patients with PNH and 27 controls. The frequency of PIG-A mutant progenitors was determined by assaying for colony-forming cells (CFCs) in methylcellulose containing toxic doses of aerolysin (1 x 10(-9) M). Glycosylphosphatidylinositol (GPI)-anchored proteins serve as receptors for aerolysin; thus, PNH cells are resistant to aerolysin. The frequency of aerolysin resistant CFC was 14.7 +/- 4.0 x 10(-6) in the bone marrow of healthy donors and was 57.0 +/- 6.7 x 10(-6) from mobilized peripheral blood. DNA was extracted from individual day-14 aerolysin-resistant CFCs and the PIG-A gene was sequenced to determine clonality. Aerolysin-resistant CFCs from patients with PNH exhibited clonal PIG-A mutations. In contrast, PIG-A mutations in the CFCs from controls were polyclonal, and did not involve T cells. Our data confirm the finding that PIG-A mutations are relatively common in normal hematopoiesis; however, the finding suggests that these mutations occur in differentiated progenitors rather than HSCs.

The authors examined frequency and patterns of self-help group attendance and active participation over a 6-month period among 411 patients receiving treatment in the NIDA Collaborative Cocaine Treatment Study. Nearly two-thirds of patients attended at least one self-help group, and nearly all of these actively participated. Alcoholics Anonymous and Narcotics Anonymous meetings were attended most frequently. Statistical analyses included chi square, one-way analyses of variance, and cluster techniques. While patterns of attendance were relatively consistent over time, findings suggest that a treatment emphasizing the importance of self-help groups is likely to encourage more self-help group attendance and participation over time.

This paper reports on the development of a 43 item rating scale that assesses therapist adherence and competence in individual drug counseling (IDC) for the treatment of cocaine dependence. Three independent judges rated 41 audiotaped IDC sessions from the pilot/training phase of the NIDA collaborative cocaine study. Judges also rated 11 tapes of Cognitive sessions and ten tapes of Supportive Expressive psychodynamic sessions. Interjudge reliability for the total scale score and subscales ranged from 0.55 to 0.89 and internal consistency coefficients ranged from 0.43 to 0.95. Ratings indicated that IDC counselors used IDC techniques more frequently and competently than did therapists from other modalities.

The classical definition of lymphohematopoietic stem cells (LHSC), the most primitive progenitors of all blood cells, requires that they have the capacity for self-renewal and for the long-term production of all blood cell lineages. However, other characteristics of LHSC have been debated. Our previous data suggested that mouse LHSC are very slowly proliferating cells that generate delayed multilineage engraftment, while "radioprotection" (rapid engraftment that will prevent early death from radiation-induced marrow aplasia) results from more committed progenitors. Alternatively, some groups have reported that mouse LHSC are responsible for both radioprotection and long-term repopulation of all blood cell lineages. A possible explanation for this difference is that cells with the capacity for long-term production of all blood cell lineages are biologically heterogeneous. We now show that 10 LHSC can generate all blood cell lineages for the lifetime of the animal. However, these cells lacked radioprotection and spleen colony-forming activity. LHSC were identified and isolated by their small size, their lack of expression of antigens characteristic of mature blood cell lineages, and their high expression of aldehyde dehydrogenase. In addition, these cells were found to express undetectable or low levels of many antigens presumed to mark LHSC, including Thy-1, Ly-6A/E (Sca-1), c-kit, and CD34. There appears to be at least two classes of LHSC with the capacity for long-term production of all blood cell lineages: one that generates both radioprotection and long-term engraftment and one that produces delayed but durable engraftment. Our data suggest that this latter class may represent a very primitive class of LHSC.

A critical determinant of the efficacy of antineoplastic therapy is the response of malignant cells to DNA damage induced by anticancer agents. The p53 tumor-suppressor gene is a critical component of two distinct cellular responses to DNA damage, the induction of a reversible arrest at the G1/S cell cycle checkpoint, and the activation of apoptosis, a genetic program of autonomous cell death. Expression of the BCR-ABL chimeric gene produced by a balanced translocation in chronic myeloid leukemia, confers resistance to multiple genotoxic anticancer agents. BCR-ABL expression inhibits the apoptotic response to DNA damage without altering either the p53-dependent WAF1/CIP1-mediated G1 arrest or DNA repair. BCR-ABL-mediated inhibition of DNA damage-induced apoptosis is associated with a prolongation of cell cycle arrest at the G2/M restriction point; the delay of G2/M transition may allow time to repair and complete DNA replication and chromosomal segregation, thereby preventing a mitotic catastrophe. The inherent resistance of human cancers to genotoxic agents may result not only by the loss or inactivation of the wild-type p53 gene, but also by genetic alterations such as BCR-ABL that can delay G2/M transition after DNA damage.

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.

BCR-ABL expression is presumed to effect clonal expansion in chronic myeloid leukemia (CML) by deregulation of cell proliferation. However, most studies have found that relative rates of cell proliferation are not increased in CML. Moreover, we found that CML progenitors display a normal proliferative response to growth factors and do not manifest greater proliferative potential than normal progenitors. Growth of malignancies depends on an imbalance between the rate of cell production and the rate of cell death. We found that BCR-ABL expression inappropriately prolongs the growth factor-independent survival of CML myeloid progenitors and granulocytes by inhibiting apoptosis, a genetically programmed process of active cell death; inhibition of BCR-ABL expression by antisense oligonucleotides reversed the suppression of apoptosis as well as the enhancement of survival. The decreased rate of programmed cell death appears to be the primary mechanism by which BCR-ABL effects expansion of the leukemic clone in CML.

Chronic myeloid leukemia (CML) is characterized by an initial chronic phase of expanded yet orderly clonal hematopoiesis that is distinguished by the BCR-ABL gene rearrangement. We found that although the mature myeloid compartment in patients with CML was expanded and entirely derived from the dominant leukemic clone, the primitive hematopoietic progenitor compartment did not show a corresponding expansion and was substantially enriched for cells without the BCR-ABL gene rearrangement. More importantly, primitive progenitors exhibiting the BCR-ABL gene rearrangement did not express either the BCR-ABL hybrid mRNA or fusion protein (P210). Expression of P210 protein and BCR-ABL mRNA increased with myeloid commitment in vivo as well as with growth factor-induced proliferation and differentiation of the primitive CML progenitors in vitro. This differential expression of BCR-ABL between primitive and mature CML progenitors may explain the expansion of the leukemic clone at the level of mature myeloid progenitors and granulocytes without a concomitant expansion of primitive CML progenitors. Because BCR-ABL mRNA is minimally expressed or may be absent in primitive CML progenitors, these cells may escape detection by reverse transcriptase-polymerase chain reaction and eradication by antisense oligonucleotides targeted against BCR-ABL mRNA.