Number Of Previous Treatments Research Articles

Switching Antidepressants After a First Selective Serotonin Reuptake Inhibitor in Major Depressive Disorder

Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first antidepressant for major depressive disorder but have response rates of 50% to 60% in daily practice. For patients with insufficient response to SSRIs, switching is often applied. This article aims to systematically review the evidence for switching pharmacotherapy after a first SSRI. A systematic literature search (updated until Feb. 10, 2005) in MEDLINE, EMBASE, CINAHL, and PsychINFO (all indexed years) identified randomized, controlled trials (RCTs) and open studies investigating switching strategies. In the absence of specific keywords for switching, we performed "sensitive" searches using free text words with wildcards ($): "switch$" or ("alternat$" adj5 "treat$") or ("alternat$" adj5 "therap$") in combination with the Cochrane Collaboration search filter for RCTs, the Cochrane Collaboration Depression Anxiety and Neurosis Group search filter for major depressive disorder, and MeSH terms for antidepressants (in combination with additional text words for all antidepressive agents). Additionally, we included 4 recent Sequenced Treatment Alternatives to Relieve Depression publications. We limited searches to adults and humans but did not apply language restrictions. Relevant articles were retrieved and critically appraised. The methodology of the studies, the results on efficacy and dropouts due to side effects, and remarks were summarized in an evidence table. Three studies comparing a switch to venlafaxine or SSRIs were pooled. Eight RCTs and 23 open studies were identified, studying populations with different levels of treatment resistance. Definitions of response and remission rates varied between studies. Observed response rates after switching to any of the classes of antidepressants varied between 12% and 86%. Remission rates varied between 7% and 82%. The number of previous treatments with antidepressants was negatively correlated with treatment outcome. Rates of dropout due to side effects varied considerably across agents (5%-39%). Switching to venlafaxine showed a modest and clinically equivocal benefit over SSRIs (number needed to treat = 13 [95% CI = 9.1 to 25.0]). After a first SSRI, any switch within or between classes of antidepressants appears legitimate (second SSRI, novel dual-acting antidepressants, selective norepinephrine or nor-adrenergic/dopaminergic agents, or tricyclic anti-depressant or mianserin). No unequivocal evidence is available to prove an advantage of a between-class switch. More guidance by randomized empirical studies is needed. Clinical implications and methodological considerations for future studies are discussed.

Mortality within 30 days of chemotherapy: a clinical governance benchmarking issue for oncology patients

No national benchmark figures exist for early mortality due to chemotherapy unlike for surgical interventions. Deaths within 30 days of chemotherapy during a 6-month period were identified from the Royal Marsden Hospital electronic patient records. Treatment intention – curative or palliative, cause of death and number of previous treatments – were documented. Between April 2005 and September 2005, 1976 patients received chemotherapy with 161 deaths within 30 days of chemotherapy (8.1%). Of these, 124 deaths (77.0%) were due to disease progression. Of the other 37 deaths, 12 (7.5%) were related to chemotherapy, six each for solid tumours and haematological malignancies, of which seven (4.3%) were due to neutropenic sepsis. For the remaining 25 deaths (15.5%) there was insufficient information. There were more deaths after third and subsequent lines of therapy than with first and secondlines of therapy. Only 12 of the 161 deaths occurred in patients who were receiving potentially curative chemotherapy to give a mortality rate in breast and gastrointestinal malignancy of 0.5 and 1.5%, respectively. It is possible to audit mortality within 30 days of chemotherapy and this should become a benchmark for standard practice nationally. Most deaths were due to disease progression in the palliative setting. We practice this form of audit each quarter and feed back to the treating teams so that deaths are discussed and practice monitored.

Expression of the corticotropin‐releasing hormone–proopiomelanocortin axis in the various clinical types of psoriasis

Psychological stress is known to aggravate inflammatory skin diseases such as atopic dermatitis, psoriasis and contact sensitivity by altering the cellular constituents of the immune system. The skin appendages function dually as prominent targets and sources of the peripheral corticotropin-releasing hormone-proopiomelanocortin (CRH-POMC) axis. In this study, we examined the expression level of CRH-POMC axis constituents in psoriasis, a well-known stress-related inflammatory skin disease. The 15 psoriasis patients and six normal controls were retrospectively selected after extensive review of their clinical records and skin biopsy specimens. We immunohistochemically analysed the expressivity of CRH, adrenocorticotrophic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various types of psoriatic lesions and control skin. A significant increase of CRH expression was observed in psoriatic lesions, which involved the entire epidermis (upper layer in particular), hair follicles and sweat glands compared with controls. Expression of ACTH and alpha-MSH was clearly stimulated in a subset of psoriasis patients compared with controls, but on the whole, lacked statistical significance. The immunoreactivity of CRH, ACTH and alpha-MSH in psoriasis was not dependent on its clinical subtype, duration or number of previous treatments. Compared with the definite increase of CRH expression in psoriasis, the expression of the POMC peptides was heterogenous with no overall significance. From the findings, we suggest that CRH, a key stress hormone, may play an important role in the pathomechanism of psoriasis.

Effects of environmental factors on multiple ovulation of zebu donors

Data on 1,294 superovulations of Brahman, Gyr, Guzerat and Nellore females were used to evaluate the effects of: breed; herd; year of birth; inbreeding coefficient and age at superovulation of the donor; month, season and year of superovulation; hormone source and dose; and the number of previous treatments on the superovulation results. Four data sets were considered to study the influence of donors’ elimination effect after each consecutive superovulation. Each one contained only records of the first, or of the two firsts, or three firsts or all superovulations. The average number of palpated corpora lutea per superovulation varied from 8.6 to 12.6. The total number of recovered structures and viable embryos ranged from 4.1 to 7.3 and from 7.3 to 13.8, respectively. Least squares means of the number of viable embryos at first superovulation were 7.8 ± 6.6 (Brahman), 3.7 ± 4.5 (Gyr), 6.1 ± 5.9 (Guzerat) and 5.2 ± 5.9 (Nellore). The numbers of viable embryos of the second and the third superovulations were not different from those of the first superovulation. The mean intervals between first and second superovulations were 91.8 days for Brahman, 101.8 days for Gyr, 93.1 days for Guzerat and 111.3 days for Nellore donors. Intervals between the second and the third superovulations were 134.3, 110.3, 116.4 and 108.5 days for Brahman, Gyr, Guzerat and Nellore donors, respectively. Effects of herd nested within breed and dose nested within hormone affected all traits. For some data sets, the effects of month and order of superovulation on three traits were importants. The maximum number of viable embryos was observed for 7-8 year-old donors. The best responses for corpora lutea and recovered structures were observed for 4-5 year-old donors. Inbreeding coefficient was positively associated to the number of recovered structures when data set on all superovulations was considered.

A phase II study of ixabepilone (BMS 247550) in metastatic renal cell carcinoma

14646 Introduction Ixabepilone (BMS) is a semi-synthetic analog of Epothilone B that functions as a microtubule stabilizer and has anti-cancer effects in several cancers including renal cell carcinoma (RCC) (Zhuang, ASCO 2004). The initial phase II study in RCC utilized a difficult and unconventional dosing schedule (6 mg/m2 IV days 1–5 every 21 days). Hence, this phase II study in RCC was designed to verify previous observations and to test the safety, feasibility, and activity of administering BMS once every 3 weeks- a schedule used in other malignancies. Methods Treatment consists of BMS 40 mg/m2 IV on day 1 every 3 weeks. Eligibility included metastatic RCC with clear or non-clear cell histology, no limits on the number of previous treatments, performance status 0–2, and normal organ function. The primary endpoint is the overall response rate by RECIST criteria on radiologic evaluation conducted every 9 weeks. Accrual to the full planned 41 patients (pts) will proceed provided that 2 or more responses are observed in the first 21 pts. Results Ten pts have enrolled (4 clear cell) with 1 declining participation prior to receiving any treatment. Eight pts have completed at least 3 cycles. Grade 3–4 toxicities include lymphopenia-2, diarrhea-2, alopecia-1, and infection-1. Grade 1–2 toxicities seen in more than 50% of pts include alopecia, neuropathy, nausea, fatigue, anemia, and lymphopenia. We have observed 1 unconfirmed partial response of short duration and 1 pt exhibited stable disease with a minor response but discontinued treatment due to excessive neurotoxicity. Three pts continue on treatment. Conclusions Toxicity at 40 mg/m2 IV on day 1 every 3 weeks is higher than previously reported with the daily x 5 schedule. While lymphopenia, diarrhea, neuropathy, and fatigue are all expected adverse events, the rates of toxicity across all grades is higher than previous reports. VHL mutation analysis is planned and will be correlated with response to therapy. Accrual and pt follow up continue. No significant financial relationships to disclose.

Reduced-intensity allogeneic stem cell transplantation for diffuse large B-cell lymphoma: Clinical evidence of a graft-versus-lymphoma effect

6546 Background: Despite being the most common non-Hodgkin’s lymphoma, there have been no specific reports on the use of reduced-intensity (RI) allogeneic stem cell transplantation (alloSCT) to treat patients (pts) with diffuse large B-cell lymphomas (DBCL). This may be due to a lack of definitive evidence for a therapeutic graft-versus-lymphoma (GVL) effect against DLBC. We undertook a retrospective analysis to assess clinical outcomes and evidence of a GVL effect in DLBC pts undergoing RI alloSCT. Methods: The analysis was limited to 18 pts with primary refractory (n = 6) or relapsed (n = 12) DLBC. The median age was 43 years (range: 31–61); median number of previous treatments was 3 (range: 2–9). Nine (50%) pts had undergone autologous transplantation. Three (16%) pts were determined to have chemo-sensitive disease to last treatment prior to RI alloSCT. All pts received a RI conditioning regimen consisting of fludarabine (30 mg/m2/d × 4d) and cyclophosphamide (1200 mg/m2/d × 4d) followed by a T-cell replete allograft from HLA-matched siblings. Results: Median potential follow-up from transplant is 43 months. Seven (39%) pts developed grade II-IV acute GVHD. Response at day +100 post-transplant was as follows: complete response (CR/CRu) = 5; partial response = 5; progressive disease = 8. Nine of 17 (53%) evaluable pts developed chronic GVHD. Median progression-free survival (PFS) was 4.8 months; however, PFS after 9 months post-transplant was 31% with 5 pts in continuous CR/CRu > 12 months post-transplant. Among 14 pts who were not in CR/CRu (n = 12) or progressed after achieving a CR/CRu (n = 2) at day +100 post-transplant, 8 (57%) subsequently achieved a CR/CRu after removal of immune suppression and/or donor lymphocyte infusion (DLI) ± chemotherapy. Seven of these 8 pts remain in continuous (median = 34 months; range: 6–55+) CR/CRu without further treatment. Median survival for all 18 pts was 19 months with survival probability of 40% plateauing at 25 months post-transplant. Conclusions: The clinical observations of sustained CR/CRu after withdrawal of immune suppression and DLI suggest that a GVL effect exists against DLBC. RI alloSCT should be considered as a treatment option for pts with primary refractory and relapsed DLBC. No significant financial relationships to disclose.

Reduced-Intensity Conditioning (RIC) Followed by Allogeneic Stem Cell Transplantation (SCT) for Relapsed Lymphomas: Impact of Pre-Transplantation Factors on Long-Term Outcome.

Allogeneic stem cell transplantation (SCT) represents a potentially curative treatment for recurrent lymphoid malignancies. In fact, potential advantages include the use of a tumor free graft and immune-mediated graft-versus-lymphoma effect. Here, we analyzed the impact of pre-transplantation factors on outcome in 141 lymphoma patients (pts) receiving RIC and allogeneic SCT from HLA-identical sibling donors. Histologic types included in the study were: low-grade non-Hodgkin lymphoma (LG-NHL; n=58), high-grade NHL (HG-NHL, n=55), Hodgkin disease (HD; n= 28). Median age was 50 years (range: 20–69). The three groups (HD vs LG-NHL vs HG-NHL) had similar characteristics in terms of: chemosensitive disease (57% vs 69% vs 67%, p=ns) and complete remission (CR) at transplant (18% vs 27% vs 34%, p=ns). Pts with HD had received more lines of chemotherapy (>2 vs ≤2) as compared to LG-NHL and HG-NHL (82% vs 52% vs 42%). Furthermore, the proportion of pts receving previous autologous SCT was significantly higher in HD and HG-NHL versus LG-NHL (75% vs 54% vs 27%). In addition, patients with HG-NHL and HD underwent frequently allo-SCT less than 2 years after diagnosis as compared to LG-NHL (58% vs 39% vs 24%). All patients received debulkying chemotherapy followed by the same RIC containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. At a median follow-up of 30 months (8–70), the overall survival (OS) and progression-free survival (PFS) were 65% (95%CI, 56–74%) and 57% (95%CI, 47%–67%), respectively. Univariate analysis showed that age (< or > 55 years), donor sex, interval between diagnosis and SCT, number of previous treatments did not influence outcome whereas diagnosis of HD was associated with a significant inferior PFS and OS. Chemosensitive disease (CR+PR) influenced PFS in HG-NHL (p<0.0003) and HD (p<0.0036) but not in LG-NHL (p=0.69). Complete remission at transplant was associated to a significant better PFS in HD (p<0.01) but not in HG-NHL (p= 0.14) and LG-NHL (p=0.7). Previous autologous SCT was associated to inferior PFS (64% vs 50%, p<0.04) but did not affected OS and TRM. By multivariate analysis, diagnosis of HD and refractory disease were associated to an inferior PFS (p<0.0001, p<0.001) whereas diagnosis of HD and no-CR at transplant remained of prognostic value on OS (p<0.006 and p<0.007). We conclude: 1) age and previous treatments, including autologous SCT, are no longer limitations for allogeneic SCT; 2) debulking therapy before RIC allogeneic SCT is required for HD and HG-NHL; 3) new strategies for an early indentification of chemorefractory pts are necessary.

Response to Treatment of Helicobacter Pylori in Patients with Immune Thromboctypenic Purpura: A Systematic Review and Metaanalysis.

Background: Patients with immune thrombocytopenic purpura (ITP) infected with Helicobacter pylori (H. pylori) are often treated with antibiotics to eradicate infection and raise platelet counts. We aimed to systematically review the evidence regarding this practice to better quantify response rate.Study Design and Methods: We searched MEDLINE through April 2005, without language restriction; reviewed reference lists and queried experts for articles describing treatment of ITP with antibiotics targeting H. pylori. We included studies of any design involving more than 5 patients. Response rates were tabulated using the authors' definitions, and pooled using a random effects model. Techniques of meta-regression were used to assess whether patient or study characteristics influenced response rates.Results: We retrieved 52 potentially eligible studies. Of these, 16 studies met our inclusion criteria. From 10 studies, we had individual level patient data. None of the studies was a controlled trial. The pooled response rate (both partial and complete responses) was 45% [95% confidence interval (C.I.) 32% to 58%]. The number of previous treatments (0–1, 2, 3 or more) influenced the response rate with an 18% (p=0.001) decline in response rate with each higher category; duration of disease did not independently predict response. In analyses of individual patient data, quartile of platelet count upon entry also influenced response rate; 58% of patients in the highest quartile responded compared to 34% in the lowest quartile (p=0.018).Conclusions: No randomized controlled trial has tested H. pylori eradication with antibiotics as a treatment for ITP. The sixteen observational studies we reviewed were fairly consistent with approximately half of treated patients having a platelet response to therapy. Without control groups, these studies do not provide strong evidence to support practice recommendations. However, given the low toxicity of antibiotic therapy, this treatment may be appropriate for patients who have not demonstrated refractoriness to multiple therapies. [Display omitted]

Efficacy of Risk Adapted Cyclophosphamide, Thalidomide and Dexamethasone in Systemic AL Amyloidosis.

The prognosis for advanced AL amyloidosis (AL) with conventional treatment remains very poor and stem cell transplantation has unacceptably high mortality (TRM). Single agent thalidomide in standard doses is poorly toleranated and has low response rates in AL (Dispenzieri et al, Amyloid 10:247; 2003) and few data on the role of thalidomide based combination chemotherapy in AL are available. We report experience with a risk adapted thalidomide based combination using cyclophosphamide and dexamethasone (CTD) in 43 patients with AL amyloidosis at the National Amyloidosis Centre, UK. The regime (adapted from the UK MRC Myeloma IX trial) consisted of a 21-day cycle oral cyclophosphamide 500mg once weekly, thalidomide 200mg/day (starting dose 100mg/day, increased after 4 weeks if tolerated) continuously and dexamethasone 40mg days 1–4 and 9–12. This was risk attenuated (CTDa) in the elderly (>70yrs), heart failure >NYHA grade II or significant fluid overload to a 28-day cycle of cyclophosphamide 500mg days 1, 8 and 15, thalidomide 200mg/day (starting dose 50mg/day, 4–weekly 50mg increments as tolerated), and dexamethasone 20mg day 1–4 and 15–18. A total on 43 patients (22M:21F, median age 61yrs, range 43–79) were treated; 35 received CTD and 8 received CTDa. Median number of organs involved was 2 (1–4), including renal in 62% of patients, cardiac in 60%, hepatic in 39%. Median follow-up from treatment initiation was 7mo (0.4–35) and from diagnosis 16.5mo (0.6–69). Patients received a median of 4 cycles of treatment (1–7). The number of previous treatments was none in 39%, one in 39%, two in 14% and three in 6%. Toxicities were seen in 17 (39%) of patients (CTDa 3; CDT 14) necessitating dose reduction in 11 (25%), dexamethasone omission in 6 (14%), thalidomide omission in 1 (2%) and complete regime discontinuation in 4 (9%). The main side effects were: worsening heart failure 20%, neuropathy 11%, infections 11%, sleepiness 2%, and neutropenia, renal impairment, constipation and fatigue − 4% each with no thrombotic complications or TRM. Survival data was evaluable in all patients while response was evaluable in 35 (81%).Haematologic response was defined as follows: complete response (CR) - sustained normalisation of sFLC (serum free light chains) ratio, partial response (PR) - sustained ≥50% reduction in pre-treatment clonal isotype. There was a haematologic response in 26 (74%). 12 (34%) has a CR, 14 (40%) had a PR, 9 (25%) had no response. sFLC assays were available after every cycle in 27pts; a reduction in the clonal class of ≥25% was evident within 30days in 59% and in another 33% by day 60. An appreciable regression of amyloid was evident in 15% of the responders by SAP scintigraphy. The median survival for the cohort has not been reached at 36 months. This preliminary study shows excellent efficacy of CTD in patients with advanced AL with response rates superior to conventional intermediate dose chemotherapy. The regime appears to be safe with no treatment related mortality and tolerance appears to be better than than standard dose thalidomide alone (Dispenzieri et al, Amyloid 10:247; 2003) or with dexamethasone (Pallidini et al, Blood 105:7; 2005). However, a quarter of the patients needed dose reduction and more stringent use of risk adaptation may improve the tolerability of this regime. Risk adapted CTD may be an alternative to standard therapies as front line treatment in AL amyloidosis.

Preliminary Report of a Phase 1 Study of CMC-544, an Antibody-Targeted Chemotherapy Agent, in Patients with B-Cell Non-Hodgkin's Lymphoma (NHL).

Introduction: CMC-544 is an antibody-targeted chemotherapy agent composed of a monoclonal antibody, which specifically targets the CD22 antigen, conjugated to calicheamicin, a potent cytotoxic antitumor antibiotic. Malignant cells of mature B-lymphocyte lineage express CD22 and thus, CMC-544 may be useful for treating lymphomas of B-cell origin.Methods: A phase 1, dose escalation trial of CMC-544 is ongoing in patients (pts) with relapsed or refractory B-cell NHL across 13 European and US sites. CMC-544 was administered intravenously every 3–4 weeks at doses of 0.4, 0.8, 1.34, 1.8, and 2.4 mg/m2. Standard safety and pharmacokinetic data and preliminary efficacy data (assessed using the International Workshop to Standardize Response Criteria for NHL) are being collected. Enrollment of pts with any type of B-cell NHL, except for Burkitt's and lymphoblastic lymphomas, was allowed in the dose escalation phase (1–6 pts per cohort). After the maximum tolerated dose (MTD) was identified, 15 pts with follicular lymphoma and 15 pts with diffuse large B-cell lymphoma will be enrolled in an expanded MTD cohort.Results: As of June 2005, 34 pts (8 women, median 71 yrs; 26 men, median 62 yrs; number of previous treatments, median 4, range 2–11) were enrolled. Dose escalation was based on 1st cycle safety evaluations of pt cohorts. Dose-limiting toxicities (DLTs) were reported for dose levels of 1.34 mg/m2 (grade 4 thrombocytopenia, 2/11 pts), 1.8 mg/m2 (bleeding requiring platelet transfusion, 1/6), and 2.4 mg/m2 (grade 4 thrombocytopenia, 1/6; grade 4 neutropenia for 7 days, 1/6). Thus, the MTD, the dose level prior to the one where ≥ 33% DLTs occurred, was 1.8 mg/m2. The most common drug-related adverse events (AEs, all grades) were: thrombocytopenia (65%), asthenia (47%), nausea (41%), neutropenia (29%), elevated liver function tests (27%), anorexia (14%), and epistaxis (12%). Grade 3–4 AEs that occurred with a frequency ≥ 10% included: thrombocytopenia (38%), asthenia (12%), and neutropenia (12%). The nadir of the thrombocytopenia was 9±2 days and platelet counts recovered spontaneously. No major bleeding episodes were reported. At the 1.8 and 2.4 mg/m2 dose levels, data suggested a dose-dependent component of platelet recovery to baseline levels and dose delays were required between successive doses. CMC-544 and total calicheamicin exposures in serum increased with dose. Clearance after 2nd or 3rd doses decreased approximately 8–14-fold compared with 1st dose, and half-life increased from approximately 1 day to 4 days. Available data suggested an association of peak CMC-544 exposures and/or total calicheamicin levels with decreases in platelet counts. Accordingly, pts in the expanded MTD cohort receive 1.8 mg/m2 CMC-544 every 4 weeks. Preliminary antitumor activity was observed in most cohorts. Complete and/or partial responses were observed in the 0.8 mg/m2 (1/3 pts), 1.34 mg/m2 (3/9), 1.8 mg/m2 (2/5), and 2.4 mg/m2 (2/5) cohorts, and in the 1st 6 pts in the expanded MTD cohort (4/6).Conclusion: CMC-544 shows promising preliminary efficacy in pts with B-cell NHL, with an associated thrombocytopenia that is clinically manageable. The expanded MTD cohort (1.8 mg/m2 every 4 weeks) continues to be enrolled.

Bendamustine/Mitoxantrone/Rituximab (BMR): A Very Effective, Well Tolerated Outpatient Chemoimmunotherapy for Relapsed and Refractory CD20-positive Indolent Malignancies. Final Results of a Pilot Study

We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m2 (80 mg/m2 in CLL) day 1 + 2, (M): 10 mg/m2 day 1 and (R): 375 mg/m2 day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 × BMR followed by 5 × BM. We have treated 54 patients with BMR. Median age was 68 years (36 - 82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1 - 7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3 - 60 + ). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.

Risk factors for acquired multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is a severe and feared problem, that is difficult to control and has shown a tendency to increase worldwide. OBJECTIVE: To analyze the risk factors for acquired MDR-TB. CASUISTIC AND METHODS: A retrospective population-based case-control study was conducted. A bacillus was considered multidrug-resistant whenever it was resistant at least to rifampin (RFP) + isoniazid (INH), and a case was considered as sensitive tuberculosis (TB) if it had undergone the first treatment during a similar period as the first treatment of an MDR-TB case, but was cured at the time of the interview. Case selection was made based on the list of Sensitivity Tests (ST) performed at the Central Public Health Laboratory of the State of Ceará, from 1990 through 1999. The Proportion Method was used to investigate resistance to the six antituberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol, ethionamide, streptomycin) used as the standard treatment in Brazil. Controls were selected from the registry of the TB Control Program. Univariate and multivariate analysis were performed, with p &lt; 0.05 considered significant. RESULTS: Out of the 1,500 STs performed during the studied period, 266 strains were multidrug-resistant; 153 patients were identified, 19 of which were excluded. The Group of Cases comprised 134 patients, and the Group of Controls comprised 185. Multivariate analysis helped to detect the following risk factors: lack of home sewer system, alcoholism + smoking, number of previous treatments, irregular treatment, and lung cavities. CONCLUSION: These five factors are important for the development of acquired MDR-TB, and an attempt to neutralize them might contribute to control TB.

A prospective controlled study of the effect of intramural uterine fibroids on the outcome of assisted conception

Although uterine fibroids occur in 30% of women and are associated with a degree of subfertility, the effect of intramural fibroids on the outcome of IVF or ICSI treatment has not been prospectively studied. Data were prospectively collected on 434 women undergoing IVF/ICSI in the assisted conception unit of an inner London teaching hospital. Patients were assessed for the presence of fibroids by transvaginal ultrasound and hysterosonography or hysteroscopy where appropriate. During the study period, 112 women with (study), and 322 women without (controls), intramural fibroids were treated. Patients were similar regarding the cause and duration of their infertility, number of previous treatments, and basal serum FSH concentration. Women in the study group were on average 2 years older (36.4 versus 34.6 years; P < 0.01). There was no significant difference in the duration of ovarian stimulation or gonadotrophin requirement, number of follicles developed, oocytes collected, embryos available for transfer or replaced. When analysing only women with intramural fibroids of < or =5 cm in size (n = 106) pregnancy, implantation and ongoing pregnancy rates were significantly reduced: 23.3, 11.9 and 15.1 respectively compared with 34.1, 20.2 and 28.3% in the control group (P = 0.016, P = 0.018 and P = 0.003). The mean size of the largest fibroids was 2.3 cm (90% range 2.1-2.5 cm). Logistic regression analysis demonstrated that the presence of intramural fibroids was one of the significant variables affecting the chance of an ongoing pregnancy, even after controlling for the number of embryos available for replacement and increasing age, particularly age > or =40 years, odds ratio 0.46 (CI 0.24-0.88; P = 0.019). This study demonstrated that an intramural fibroid halves the chances of an ongoing pregnancy following assisted conception.

Cyclophosphamide/Fludarabine (CF) is Active in the Treatment of Mantle Cell Lymphoma

The purpose of this study was to determine the efficacy and toxicity of the cyclophosphamide and fludarabine (CF) regimen in patients with newly diagnosed and relapsed/refractory mantle cell lymphoma (MCL). Thirty patients with pathologically confirmed MCL were treated with the CF regimen. Ten (33%) had no prior therapy, six (20%) had one previous regimen, and 14 (47%) received two or more prior regimens. Ninety cycles of CF with a median of 3 cycles/patient (range, 1–5 cycles) were administered to patients with MCL. Nine patients (30%) had a complete response (CR) and 10 (33%) had a partial response (PR) for an overall response rate (RR) of 63%. The median failure-free survival (FFS) and overall survival (OS) was 4.8 months and 17.5 months, respectively. When patients were analyzed based upon the number of previous treatments (0,1, or 2 or more), those with no previous treatment (n=10) had an overall response of 100%, with 70% CR. The median FFS was 28.1 months and the median OS for this group has not been reached at 42.3+ months. Hematologic and infectious toxicity were the major toxicities encountered with the CF regimen. Grade 3–4 neutropenia, thrombocytopenia and anemia were seen in 50%, 37%, and 36% of patients, respectively. There were 13 episodes of grade 3 infections. There was no treatment related mortality. In conclusion, the high response rate associated with the CF regimen merits further investigation in previously untreated patients with MCL, particularly in those who are not candidates for aggressive therapy.

Characteristics of American-Indian clients seeking inpatient treatment for substance abuse.

The current study was conducted as a preliminary examination of substance use and some of its correlates in nonreservation-residing American Indians. A group of 522 American-Indian (AI) subjects (473 men) were compared with two sets of geographic controls: (1) an equal number of African Americans (AA) and (2) an equal number of European Americans (EA). All received treatment in the same facilities over the same time period. Contrary to expectations, the ethnic/racial groups were remarkably similar on a number of alcohol use variables, including the amount consumed in the 6 months prior to treatment and the number of previous treatments. Among those self-reporting as problem drinkers, there were group differences in the age of first drink (AA mean = 13.54, AI mean = 12.24 and EA mean = 11.71) and first drunk (AA mean = 15.80, AI mean = 14.23 and EA mean = 14.08) and the number of alcohol-related problems (AA mean = 7.52, AI mean = 8.49 and EA mean = 8.46). On these measures, AI and EA subjects did not differ whereas AA subjects reported a later age of onset and fewer negative consequences. EA and AI male subjects reported marijuana as their most frequently used "other" drug, whereas AA male subjects listed stimulants as their primary drugs. Regardless of ethnic/racial group, women did not differ on their drug(s) of choice, reporting stimulants as the most frequently abused drug (after accounting for alcohol use). This preliminary study is remarkable for the observed similarities among groups. Future studies using more rigorous sampling are needed to provide clarification of this preliminary study.

Cultural differences on three measures of dissociation in a substance abuse population.

Scores on three measures of dissociation were compared between 48 African American and 48 Caucasian men being treated for substance abuse at a VA Medical Center. The three assessment instruments included the Dissociative Experience Scale, the Questionnaire of Experiences of Dissociation, and the North Carolina Index of Dissociation. Groups were matched with respect to age, education, marital status, number of previous treatments, IQ, employment status, history of childhood abuse, and psychological discomfort. In each case, the African-American group scored higher, with statistical significance being achieved on two of the three instruments. Potential implications of these findings were discussed and future research was suggested.

Cultural differences on three measures of dissociation in a substance abuse population

Scores on three measures of dissociation were compared between 48 African American and 48 Caucasian men being treated for substance abuse at a VA Medical Center. The three assessment instruments included the Dissociative Experience Scale, the Questionnaire of Experiences of Dissociation, and the North Carolina Index of Dissociation. Groups were matched with respect to age, education, marital status, number of previous treatments, IQ, employment status, history of childhood abuse, and psychological discomfort. In each case, the African-American group scored higher, with statistical significance being achieved on two of the three instruments. Potential implications of these findings were discussed and future research was suggested. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 1109–1116, 1998.

Remission of substance use disorder among psychiatric inpatients with mental illness.

The authors assessed the nature and stability of remission of substance use disorder among persons with severe mental illness at index hospitalization and at 1-year follow-up. Consecutively admitted inpatients with severe mental illness completed the Structured Clinical Interview for DSM-III-R, Quality of Life Interview, and Addiction Severity Index at admission and 1 year later. Of the 268 patients, 70 were classified as past substance abusers in remission at baseline. Baseline characteristics and 1-year outcomes of this group were compared with those of the 109 current substance abusers and the 89 patients who were not substance abusers. The past abusers were significantly more likely to be women, and they consistently differed significantly from the current abusers in variables involving frequency of drug and alcohol use at baseline. During the follow-up period, the patients with current abuse at baseline were significantly more likely to have recurrences of substance use disorders and to use substance abuse services, and they had significantly more months of alcohol use and alcohol use to excess during follow-up than did the past abusers. Baseline and follow-up assessments suggested that a substantial proportion of severely mentally ill patients with past substance use disorders are in stable remission.

Demographic evaluation of successful antipsoriatic climatotherapy at the Dead Sea (Israel) DMZ Clinic

Natural balneologic properties, thermomineral springs and unequivocal success in improving psoriasis, attract an ever-growing number of psoriatics to the DMZ Clinic on the shores of the Dead Sea in Israel. This paper analyses the rate of success of this balneotherapy in 740 psoriatics who flew in from Germany specifically for this treatment, during 1995, as a function of sex, family history of the disease, number of previous treatments at the Dead Sea, skin type, skin involvement, joint involvement, duration of treatment, sun-exposure schedule, remission length, and psychologic supervision. After 4 weeks, 70% of the patients were completely cleared, this improvement being about the same across both sexes. Family history of the disease, skin type, and psychologic support did not affect the rate of success. On the other hand, previous treatments at the Dead Sea, moderate to severe skin surface involvement, and participation of arthritis, improved the chance of better clearing of the psoriatic condition. Similar improvement was obtained by a longer sun-exposure schedule and a complete-4-week treatment. These results indicate that the medical improvement in the psoriatic condition after a 4-week stay at the Dead Sea can be better enhanced and its remission prolonged if additional demographic and anamnestic factors are carefully taken into account.

High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease--a pragmatic prognostic index.

High-dose chemotherapy with autologous bone marrow transplantation is used in the treatment of relapsed or high-risk Hodgkin's disease. As prospective randomised studies have proved difficult to accrue to, current recommendations are based on the reports of large series of prospectively collected data. We have looked at the outcome of 89 patients treated in this way at a single institution and have developed an index to predict outcome. Of 89 patients, with a median age of 29 years (range 15-51 years), eight patients were in first complete remission/partial remission (CR/PR), 17 in second or later CR, 37 were responding relapses, 13 resistant relapses, 11 primary refractory and three untested relapses. Combinations of melphalan, BCNU and etoposide were given in all cases except in ten patients who received melphalan alone. The median follow-up was 43 months (range 6-77 months). A total of 24 patients were in CR at the time of autologous bone marrow transplantation (ABMT), 33 achieved CR with ABMT, 16 PR, to give a response rate to ABMT of 49/65 = 74% (95% CI 60-83%) with a CR rate of 51% (CI 36-62%). In a Cox's multivariate analysis the most important factors in predicting outcome after ABMT were response to treatment before entry, number of previous treatments and previous chemosensitivity. Using these factors we devised a prognostic index which reliably selects a group of patients (65%) with at least a 70% chance of being progression free from 1 year onwards. Patients who have never achieved a CR and have received three or more chemotherapy regimens do not benefit from high-dose chemotherapy as used in this study.