Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors.

A series of 4-alkenyl and 4-alkynyl-3, 4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones were found to be potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of human immunodeficiency virus type-1 (HIV-1). The 4-alkenyl-3, 4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones DPC 082 and DPC 083 and the 4-alkynyl-3, 4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones DPC 961 and DPC 963 were found to exhibit low nanomolar potency toward wild-type RF virus (IC(90) = 2.0, 2.1, 2.0, and 1.3 nM, respectively) and various single and many multiple amino acid substituted HIV-1 mutant viruses. The increased potency is combined with favorable plasma serum protein binding as demonstrated by improvements in the percent free drug in human plasma when compared to efavirenz: 3.0%, 2.0%, 1.5%, 2. 8%, and 0.2-0.5% for DPC 082, DPC 083, DPC 961, DPC 963, and efavirenz, respectively.

Novel 2,2-dioxide-4,4-disubstituted-1,3-H-2,1,3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors.

Benzothiadiazine non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV have been synthesized via a novel process to afford active inhibitors, with the most potent compound exhibiting an IC90 = 180 nM in a whole cell assay. The 2,2-dioxide-1H-2,1,3-benzothiadiazine ring system was constructed in one step from 2-amino-5-chlorobenzonitrile.

Changes in antimicrobial resistance among Salmonella enterica Serovar typhimurium isolates from humans and cattle in the Northwestern United States, 1982-1997.

We compared antimicrobial resistance patterns of Salmonella enterica serovar Typhimurium (ST) of isolates from humans (n = 715) and cattle (n = 378) in the Pacific Northwest from 1982 through 1997. The major changes in antimicrobial resistance can be attributed to the widespread clonal dissemination of multidrug-resistant definitive phage type 104 ST.

The relationships between premilitary school record data and risk for posttraumatic stress disorder among Vietnam war veterans.

The purpose of this study was to determine whether Vietnam veterans' risk for posttraumatic stress disorder (PTSD) was correlated with their premilitary school performance. The authors compared both primary and secondary school record data on hospitalized chemically dependent PTSD patients with those of both non-PTSD, chemically dependent and community controls. All participants were male Vietnam war combat veterans. The comparisons were made with MANCOVA analyses with the effects of combat and age differences between groups controlled. For the most part, primary-school grade point average, absenteeism, and tardiness data on three groups did not differ significantly. However, the mean secondary school grade points of the future PTSD patients were generally substantially lower than those of controls. Additionally, more secondary school absenteeism and tardiness were reported among future PTSD patients than in the controls. The groups did not differ significantly on number of extracurricular activities. Academic weakness, absenteeism, and tardiness in secondary school appear to be moderately strong predictors of vulnerability to PTSD after traumatization. It also supports the claim that chronic PTSD is, in part, the result of weaknesses present before exposure to trauma.

The efficacies of three relaxation regimens in the treatment of PTSD in Vietnam War veterans.

Ninety male Vietnam veterans with posttraumatic stress disorder (PTSD) were administered relaxation instructions, relaxation instruction with deep breathing exercises, or relaxation instructions with deep breathing training and thermal biofeedback. Improvement appeared on only 4 of the 21 PTSD and physiological dependent variables studied. All 21 Treatment x Time interactions were nonsignificant. This suggests that the treatments were mildly therapeutic, but that the additions of training in deep breathing and thermal biofeedback did not produce improvement beyond that associated with simple instructions to relax in a comfortable chair.

A comparison of the symptoms associated with early and late onset alcohol dependence.

This study was designed to determine whether the prevalences of the DSM-III alcohol abuse/dependence symptoms in 87 early and 73 late onset male alcoholics differ from one another. The authors administered a 19-item alcohol abuse/dependence symptom checklist with items based on the DSM-III criteria. Nine of the 19 symptoms were reported significantly more often in the early than in the late onset alcoholics. Antisocial behaviors were reported to have been particularly frequent in the early onset group.

A comparative outcome study of frequent, moderate, occasional, and nonattenders of Alcoholics Anonymous.

The purpose of this project was to identify the outcomes associated with frequent, moderate, occasional, and nonparticipation in Alcoholics Anonymous by male alcohol dependents during the first month after treatment. Informants reported nonparticipants consumed far more alcohol during a 48 week followup than moderate or occasional participants. Moderate and occasional participants were rated as abstinent more often than nonparticipants. Nonparticipants were also reported jailed more often than participants. All other consumption and quality of life comparisons between the groups were nonsignificant. Occasional and moderate AA attendance appear to be associated with better outcomes than nonattendance, but frequent participation was not associated with additional improvement.

A 48-week natural history follow-up of alcoholics who do and do not engage in limited drinking after treatment.

The research on the controversial Alcoholics Anonymous tenet that limited drinking rapidly leads alcoholics to inebriety is inconclusive. We conducted 48-week follow-ups on 51 posttreatment alcohol dependents who had reportedly engaged in limited drinking and 51 paired controls who apparently had not. According to the informants, the limited drinkers consumed 16 times as much alcohol and were 4 times as likely to regress to unacceptable drinking as controls. They were also more often rehospitalized and attended fewer Alcoholics Anonymous meetings than the controls. They were, however, usually (62%) categorized as abstinent or moderate drinkers when assessed during the follow-up period. The groups did not differ in risk of jailing, detoxification, or job loss, nor did limited drinkers ordinarily regress quickly to inebriety. The outcomes of our limited drinkers were inferior to those of controls but much less negative than those Wilson's Alcoholics Anonymous maintains.

Social maladjustment indicators in PTSD patients' families of origin.

We compared the frequencies with which PTSD patients, psychiatric controls, and hospital employee controls reported that their fathers, mothers, and oldest siblings of each sex had been incarcerated or had received psychiatric/psychological treatment. We also compared estimates of the number of psychiatric hospitalizations, incarcerations, courses of outpatient treatment, treatment sessions, and days of institutionalization undergone by the relatives. Only a chance number of significant differences appeared, which suggests that general psychosocial maladjustment in one's family of origin does not appear to increase trauma survivors' risk for PTSD.

Posttraumatic stress disorder (PTSD) symptoms in PTSD patients' families of origin.

Posttraumatic stress disorder (PTSD) patients, psychiatric controls, and hospital employee controls rated their father, mother, and oldest sibling of each sex on 14 PTSD Interview (PTSD-I) symptom ratings. The stress disorder patients assigned their relatives significantly higher PTSD-I ratings than the control group members did in 35 of 120 comparisons. The number of significant differences was nearly identical in the fathers, mothers, sisters, and brothers. Differences were particularly frequent on items pertaining to intrusive thoughts, impoverished relationships, and guilt. The results suggest that a trauma survivor's risk for PTSD may be related to his family's history for PTSD-like behaviors.

Comparative concurrent validities of five alcoholism measures in a psychiatric hospital.

The concurrent validities of five self-report alcoholism measures were compared in a psychiatric hospital population using Diagnostic Interview Schedule (DIS) alcohol dependence module outputs as criterion. The Michigan Alcohol Screening Test was the most accurate identifier of alcohol dependence at some point in the subjects' life, while the CAGE interview best identified alcohol dependence in the previous year. The correlations of a quantity-frequency measure, the Clinical Signs checklist, and the Medical History questionnaire with DIS alcohol dependence module outputs were generally weaker. The data also suggested that cutting scores based on local norms may offer better hit rates in psychiatric settings than those proposed by the instruments' authors, but additional cross-validations are needed to confirm that possibility.

Effects of a Vietnam War Memorial pilgrimage on veterans with posttraumatic stress disorder.

We compared the scores of Vietnam veterans in treatment for posttraumatic stress disorder on the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder just before, just after, and 6 months after they participated in a pilgrimage to the Vietnam War Memorial in Washington, DC. Significant short-term improvement was reported on Mississippi total scores and on 10 of its 35 items. The number of items showing significant improvement between the initial assessment and the 6-month follow-up did not exceed chance, but significant variance increases appeared on 8 of 35 items. This suggests that the pilgrimage led to a) short-term improvements on several posttraumatic stress disorder symptoms and b) long-term improvements for some participants, but equally large exacerbations for others on a subset of symptoms.

A comparison of combat's effects on PTSD scores in veterans with high and low moral development.

This study was designed to explore the effects of moral development on the relationship between combat intensity and severity of posttraumatic stress disorder. The effect of combat intensity on PTSD Interview total scores and several individual stress disorder symptom ratings was substantial in a Low Moral Development sample, but negligible in a High Moral Development group. These data suggest that moral development may blunt the effect of combat severity on PTSD. These effects were strongest on items that describe reexperiencing of the trauma and exaggerated arousal. Possible interpretations of the results and several caveats were discussed.

Geophysical variables and behavior: XXXIII. Onsets of historical and contemporary poltergeist episodes occurred with sudden increases in geomagnetic activity.

Several researchers have reported that poltergeist episodes frequently begin on the day (+/- 1 day) of a sudden and intense increase in global geomagnetic activity. To test this visual observation, a near-complete account of these episodes for which the inception dates were recorded and verified was examined. Statistical analyses clearly indicated that global geomagnetic activity (aa index) on the day or day after the onset of these episodes was significantly higher than the geomagnetic activity on the days before or afterwards. The same temporal pattern was noted for historical cases and for those that have occurred more recently. The pattern was similar for episodes that occurred in North America and in Europe. The results were statistically significant and suggest that these unusual episodes may be some form of natural phenomena that are associated with geophysical factors.