[B symptoms in unexplained mediastinal lymphadenopathy : Case report of a 72-year-old male patient with VEXAS syndrome]. / B-Symptomatik bei unklarer mediastinaler Lymphadenopathie : Fallbericht eines 72-jährigen Patienten mit VEXAS-Syndrom.

The case of a 72-year-old male patient who presented to our centre for rare diseases with recurrent fever, night sweats and weight loss with initially confirmed mediastinal lymphadenopathy is reported. Investigation of lymph node material was unrevealing. As an additional finding, the patient had a myelodysplastic syndrome. VEXAS syndrome (vacuoles, E1 enzyme, X­linked, autoinflammatory, somatic) could be confirmed on the basis of a bone marrow biopsy and genetic testing.

Therapy satisfaction and health literacy are key factors to improve medication adherence in systemic sclerosis.

OBJECTIVE: Although medication adherence (MA) contributes to therapeutic outcome in systemic sclerosis (SSc), research data are scarce. Factors influencing MA in SSc are hardly known. METHOD: We conducted a monocentric, cross-sectional study on 85 patients with SSc at the University of Lübeck, Germany, using the Compliance Questionnaire of Rheumatology as the main measurement tool of MA. We also used the Scleroderma Health Assessment Questionnaire, Illness Perception Questionnaire - Revised, Health Literacy Questionnaire, Lübeck Medication Satisfaction Questionnaire (a novel instrument created for this study), and patients' demographic and clinical data, to find factors contributing to MA. RESULTS: Good MA was seen in 51.8% of patients. MA was positively associated with therapy satisfaction (p < 0.001), modified Rodnan Skin Score (p = 0.032), age (p = 0.025), intake of micronutrients (p = 0.033), number of prescribed drugs (p = 0.014), and some dimensions of health literacy. Negative associations were found for patients with weight loss attributed to SSc (p = 0.009) and the perception that the disease is caused by the patient's personality (p = 0.011) or emotional state (p = 0.037). CONCLUSION: Although most SSc patients display good MA, non-adherence remains a major problem. Patients should be assessed for non-adherence. The factors affecting MA identified herein could help to improve therapeutic outcomes.

[The unusual mimicker of a polymyositis]. / Der außergewöhnliche Nachahmer einer Polymyositis.

This article describes a hantavirus-associated pronounced myositis as a rare differential diagnosis to polymyositis. The literature on the pathogenesis of hantavirus disease discusses less a direct viral cytopathology but more a secondary immune dysregulation with induction of a capillary leak. This article describes for the first time a case of successful treatment of protracted hantavirus myositis using high-dose glucocorticoids and cyclophosphamide, followed by ciclosporin and MTX.

[De-escalation of therapy in ANCA-associated vasculitides]. / Therapiedeeskalation bei ANCA-assoziierten Vaskulitiden.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) require a differentiated therapeutic approach depending on the degree of organ dysfunction and disease activity. In organ dysfunction and life-threatening AAV cyclophosphamide and rituximab are recommended for the induction of remission. For remission induction with a lack of organ dysfunction and non-life-threatening AAV, methotrexate or mycophenolate mofetil are recommended. For remission maintenance therapy azathioprine or methotrexate are used. In the case of contraindications, intolerance or previous failure of azathioprine and methotrexate treatment, rituximab, leflunomide or mycophenolate mofetil may be used as alternatives. Maintenance therapy is usually continued for at least 2 years. De-escalation of therapy requires continuous clinical monitoring while the glucocorticoid medication and immunosuppressive therapy is tapered; however, every de-escalation of therapy carries a risk of relapse.

Diagnostic Value of Procalcitonin in ANCA-Associated Vasculitis (AAV) to Differentiate Between Disease Activity, Infection and Drug Hypersensitivity.

OBJECTIVE: Procalcitonin (PCT) is considered to be a specific marker for severe bacterial infections and sepsis. Elevated PCT levels have been reported in active autoimmune diseases without infection. The aim of this study was to assess the diagnostic value of PCT serum levels in ANCA-associated vasculitis (AAV) patients with respect to infection, disease activity and drug fever using a high sensitive PCT detection method. METHODS: In 53 AAV patients with elevated C-reactive protein (CRP) PCT was determined by the Thermo Scientific BRAHMS PCT sensitive KRYPTOR assay. Patients underwent standardized diagnostic procedures for evaluation of disease activity and infection. RESULTS: 53 patients with AAV and elevated CRP (7.7±6.9 mg/dl, PCT 0.34±1.02 ng/ml) were assessed, 10 had infection with elevated CRP levels of 11.2±10.2 mg/dl and PCT levels of 1.06±2.07 ng/dl. 43 patients had no evidence of infection, 36 of them were presented with AAV with normal or only slightly positive PCT levels in active disease (n=36) (PCT 0.06±0.06 ng/ml). 7 patients had increased PCT levels due to azathioprine hypersensitivity (0.76±1.01 ng/ml). For discrimination between infection and vasculitis activity PCT was more useful than CRP with the best cut-off at 0.1 ng/ml (sensitivity 60%, specificity 92%). CONCLUSION: In contrast to previous studies using semiquantitative PCT assays, the KRYPTOR performs better with respect to discrimination of infection from active AAV. In all patients assessed with active AAV (and without infection) PCT levels remained below the PCT reference limit (0.5 ng/ml) for infections. Drug hypersensitivity seems to be an important differential diagnosis in the setting of elevated CRP and PCT in patients who receive azathioprine.

[Risk of infection by biologics]. / Infektionsrisiko durch Biologika.

Tumor necrosis factor (TNF-alpha) plays an essential role in the orchestration of inflammatory processes including autoimmune disorders, host defence and granuloma formation. TNF antagonists are highly effective in the therapy of rheumatoid arthritis, but they compromise host defence mechanisms, especially concerning bacterial infections inducing granuloma formation, such as tuberculosis. Other biologics have been developed and approved for the therapy of rheumatoid arthritis, e.g. an interleukin (IL-1) blocking agent (anakinra), an antibody that depletes CD20 positive B-cells (rituximab) and an inhibitor of T-cell co-stimulation (abatacept). In spite of initial skepticism regarding side effects, such as an increased risk of infections, biologics now play an essential role in the therapy of autoimmune diseases due to the implementation of efficient screening measures concerning side effects (such as reactivation of tuberculosis). This review summarizes the current available data regarding risk of infection and gives and overview on recommended screening, contraindications and events that require withdrawal of therapy.

Value of whole-body washing with chlorhexidine for the eradication of methicillin-resistant Staphylococcus aureus: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Whole-body washing with antiseptic solution has been widely used as part of eradication treatment for colonization with methicillin-resistant Staphylococcus aureus (MRSA), but evidence for the effectiveness of this measure is limited. OBJECTIVE: To study the efficacy of whole-body washing with chlorhexidine for the control of MRSA. DESIGN: Randomized, placebo-controlled, double-blinded clinical trial. SETTING: University Hospital of Heidelberg and surrounding nursing homes. PATIENTS: MRSA carriers who were not treated concurrently with antibiotics effective against MRSA were eligible for the study. INTERVENTION: Five days of whole-body washing with either 4% chlorhexidine solution (treatment group) or with a placebo solution. All patients received mupirocin nasal ointment and chlorhexidine mouth rinse. The outcome was evaluated 3, 4, 5, 9, and 30 days after treatment with swab samples taken from several body sites. RESULTS: Of 114 patients enrolled in the study (56 in the treatment group and 58 in the placebo group), 11 did not finish treatment (8 from the treatment group and 3 from the placebo group [P=.02]). At baseline, the groups did not differ with regard to age, sex, underlying condition, site of MRSA colonization, or history of MRSA eradication treatment. Eleven patients were MRSA-free 30 days after treatment (4 from the treatment group and 7 from the placebo group [P=.47]). Only groin-area colonization was significantly better eradicated by the use of chlorhexidine. The best predictor for total eradication was a low number of body sites positive for MRSA. Adverse effects were significantly more frequent in the treatment group than in the placebo group (any symptom, 71% vs 33%) but were reversible in most cases. CONCLUSION: Whole-body washing can reduce skin colonization, but it appears necessary to extend eradication measures to the gastrointestinal tract, wounds, and/or other colonized body sites if complete eradication is the goal.

Impairment of lung function, health status and functional capacity in patients with ANCA-associated vasculitis.

OBJECTIVE: To determine the effects of lung involvement on respiratory function in patients with ANCA-associated vasculitis and the relation to impaired health status. METHODS: Thirty patients with ANCA-associated vasculitis in remission (15 with lung involvement at diagnosis as determined by an abnormal chest X-ray) were examined. We measured lung function, skeletal muscle strength [quadriceps force (QF), respiratory muscle strength (Pi(max))], exercise capacity (VO(2) peak) using treadmill exercise tests, and health status using the Short Form 36 and St George's respiratory questionnaires. RESULTS: Exercise capacity was reduced compared with predicted values (58.2%, range 23-123%) and 18 patients showed functional aerobic impairment. Respiratory muscle function was reduced (72.1% predicted, range 20-108%) and was not related to lung involvement or steroid usage. Transfer factor correlated significantly with exercise capacity, suggesting inadequate delivery of oxygen to muscles. Nine patients had reduced transfer factor (seven with lung involvement). Patients with lung involvement had impaired gas transfer compared with those without lung involvement (96.9 +/- 6 vs 113.3 +/- 4.7% predicted, P = 0.04). However, there were significant abnormalities in other lung function parameters not related to previous lung involvement (eight patients had reduced forced expiratory volume in 1 s, and five patients had reduced residual volume). Twelve patients (five with previous lung involvement) had obstructive airways disease. Physical health status was impaired to a greater degree than mental health status across the whole group and was not related to lung involvement or original disease severity, but correlated with transfer factor. CONCLUSION: Patients with ANCA-associated disease may have significant lung function impairment irrespective of lung involvement at the time of diagnosis. Patients showed reduced respiratory muscle strength, health status and exercise capacity, which correlated with reduced transfer factor.

BPI-ANCA in transporter associated with antigen presentation (TAP) deficiency: possible role in susceptibility to Gram-negative bacterial infections.

Although HLA class I expression is diminished in patients with defects in the transporter associated with antigen presentation (TAP), recurrent Gram-negative bacterial lung infections are found from childhood onwards. As MHC class II-mediated responses are normal, other mechanisms that contribute to susceptibility to infections are presumed. The bactericidal/permeability-increasing protein (BPI) is a potent neutrophil antibiotic that neutralizes endotoxin efficiently. As antineutrophil cytoplasmic autoantibodies (ANCA) against BPI were found in the majority of cystic fibrosis patients and correlate with disease severity we examined the prevalence of BPI-ANCA and their contribution to susceptibility to bacterial infections in six TAP-deficient patients. Although only two patients showed ANCA in indirect immunofluorescence, BPI-ANCA occurred in five of six patients in ELISA. Purified IgG from BPI-ANCA-positive sera (five of six) inhibited the antimicrobial function of BPI in vitro. Epitope mapping revealed binding sites not only on the C-terminal but also on the antibiotic N-terminal portion of BPI, indicating that short linear BPI peptide fragments may be long-lived enough to become immunogens. In conclusion, BPI-ANCA are associated strongly with TAP deficiency. Inhibition of the antimicrobial BPI function by BPI-ANCA demonstrates a possible mechanism of how autoantibodies may contribute to increased susceptibility for pulmonary Gram-negative bacterial infections by diminished bacterial clearance.

Preventing substance use among Native American youth: three-year results.

This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth. After completing pretest measurements, 1,396 third- through fifth-grade Native American students from 27 elementary schools in five states were divided randomly by school into two intervention arms and one control arm. Following intervention delivery, youths in all arms completed posttest measurements and three annual follow-up measurements. Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention. One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth. Outcome assessment batteries measured youths' reported use of smoked and smokeless tobacco, alcohol, and marijuana. Over the course of the 3.5-year study, increased rates of tobacco, alcohol, and marijuana use were reported by youths across the three arms of the study. Though cigarette use was unaffected by intervention, follow up rates of smokeless tobacco, alcohol, and marijuana use were lower for youths who received skills intervention than for youths in the control arm. Community intervention components appeared to exert no added beneficial influence on youths' substance use, beyond the impact of skills intervention components alone. Finally, gender differences were apparent across substances, measurements, and study arms, with girls smoking more cigarettes and boys using more smokeless tobacco, alcohol, and marijuana.

Phase II trial of combination intraperitoneal cisplatin and 5-fluorouracil in previously treated patients with advanced ovarian cancer: long-term follow-up.

OBJECTIVES: This trial was performed to determine the response rate and progression-free and overall survivals of patients with advanced recurrent ovarian cancer who were treated with intraperitoneal cisplatin and 5-fluorouracil. METHODS: Twenty-four patients with ovarian cancer were entered on this trial and treated with intraperitoneal (ip) cisplatin (DDP) and ip 5-fluorouracil, every 3 weeks for eight cycles. Following iv hydration, the cisplatin and 5-fluorouracil were administered through an ip catheter in 2 liters of 0.9% normal saline with a 4-h dwell. RESULTS: All patients were evaluable for progression-free and overall survival and toxicity analysis, and 22 patients for response. The median age was 59 (range, 35-71); initial disease status included 9 patients with residual disease following chemotherapy prior to entry on this study; 5 patients had progressed, and 10 patients had recurrent disease more than 6 months following initial chemotherapy. Of the 9 patients with residual disease, 1 complete response and 3 partial responses were observed; of 10 patients with recurrent disease, 1 complete and 1 partial response were observed for an overall response rate of 27%. No objective responses were seen in the 7 patients who were platinum-refractory on protocol entry. The median progression-free and overall survivals are 7.0 (range, 0.5-137) and 15.5 (range, 3-147) months, respectively. Toxicity included hypomagnesemia, vomiting, abdominal pain, and mild anemia. Only one patient required a dosage adjustment of cisplatin for a serum creatinine elevation >2.0 mg/dl. CONCLUSIONS: We conclude that the combination of ip cisplatin and 5-FU is an effective regimen for patients with residual or relapsed epithelial ovarian cancer with survival durations, response rates, and toxicity profiles that compare favorably with those of other second-line ovarian cancer regimens. Patients who are primarily platinum-refractory are unlikely to benefit from these agents administered into the peritoneal cavity.

Enhancing the educational achievement of at-risk youth.

This study examined a non-school program aimed at enhancing the educational performance of economically disadvantaged early adolescents who live in public housing. The educational enhancement program included discussions with adults, writing activities, leisure reading, homework, helping others, and games using cognitive skills. A three-arm research design juxtaposed program youth who received educational enhancements with comparison youth in affiliated facilities who did not receive the program and with control youth in other community programs without educational enhancements. From youths, follow-up data collected 2 1/2 years after baseline revealed uniformly positive outcomes for program youth on measures of reading, verbal skills, writing, and tutoring. Teacher reports at final follow-up favored program and comparison youth over controls on measures of reading, writing, games, overall school performance, and interest in class material. School grades were higher for program youth than for comparison and control youth for reading, spelling, history, science, and social studies. Overall grade averages were higher for program youth versus comparisons and controls, as was school attendance. Study data lend empirical support to the provision of educational enhancements in non-school settings for at-risk youths.

Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up.

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.

Organizational and individual factors influencing job satisfaction and burnout of mental health workers.

Job satisfaction and burnout are important areas of study because of the financial and social effects of job satisfaction and the damaging physical/psychological impacts of burnout. Two hundred family/children and psychiatric workers of seven social service organizations were surveyed. Instruments used were the Minnesota Satisfaction Questionnaire, the Maslach Burnout Inventory, and the Staff Burnout Scale for Health Professionals. Reported levels of job satisfaction and burnout are within normal limits. Psychiatric and family/children workers report equal job satisfaction levels, but the latter group reports significantly higher burnout levels. Both groups are particularly satisfied with the amount of praise delivered by supervisors and are reportedly dissatisfied with salary levels and promotional opportunities. These three factors are strongly associated with job satisfaction and burnout levels of both groups. Findings have practical implications for social service administrators and practitioners. Correlates of satisfaction and burnout can be altered in order to maintain employee satisfaction and reduce burnout, absenteeism and turnover.

Psychosocial determinants of alcohol use among minority youth living in public housing developments.

Youth residing in low income, inner city, public housing developments might be extremely vulnerable to psychosocial risk factors associated with alcohol use. In this study, we developed and tested a model of alcohol etiology with 624 African-American and Hispanic 7th graders residing in public housing developments. The students completed questionnaires concerning their alcohol use, social influences on their drinking, their drinking attitudes and knowledge, their psychosocial skills, and demographic and behavioral control information. Logistic regression analyses indicated that social influences from adults, friends, and family members predicted alcohol use. Individual psychosocial characteristics, e.g., drinking refusal, lowered the odds of drinking. These findings imply that effective prevention approaches targeting minority urban youths residing in public housing developments should provide them with an awareness of social influences to drink, correct misperceptions concerning the prevalence of drinking, and train them in relevant psychosocial skills.

Preventing teenage pregnancy: translating research knowledge.

PIP: This paper explores the multiple dimensions of teenage pregnancy and suggests ways on how to prevent it. It reviews the contemporary historical context and the epidemiology of adolescent pregnancy, and describes past and promising approaches to its prevention. Although teenage pregnancy has long been recognized as a social problem by Americans, policymakers, and social scientists, little progress has been made to understand its social and behavioral origins. Previous efforts to delay conception and childbearing among adolescents have done little in changing the nature of the problem. However, recent studies are starting to discover not only the underlying causes of pregnancy among adolescents, but also the appropriate strategies for reducing the risks of unplanned teenage pregnancy. Such strategies include the use of theory-based interventions which can explain the sexual risk-taking that often leads to unplanned pregnancies among adolescents and interventions that consider cultural differences. Promising approaches are those that address the several dimensions of the problem and the social and behavioral contexts in which it occurs.^ieng

Reducing cancer risk among Native American adolescents.

BACKGROUND: This article discusses the development, implementation, and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States. METHODS: The intervention outcome study includes a research design and outcome measurement instruments. In collaboration with Native American communities, reservations, and organizations in the Northeastern United States, implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention. RESULTS: Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising, and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest. Youths in the combined intervention were significantly less apt to report smoking of any kind. Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items. As for dietary variables, pretest to posttest measurement scores showed that, after receiving the curriculum, youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implications of consuming dietary fat, fiber, fruits, and vegetables. Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practices, cultural dietary habits, and healthy food choices available for Native American cultures. Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions. CONCLUSIONS: Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns. In particular, results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths' knowledge and attitudes with regard to tobacco use and diet. Further, the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum.

Adaptive health behaviors among ethnic minorities.

Race, ethnicity, and cultural attitudes and practices are among the variables that influence health behaviors, including adaptive health behaviors. The following discussions highlight the important role of social conditions in shaping health behaviors and the central role of family in promoting health across the Asian, Hispanic, Native American, and African American ethnic groups. Factors that may lead to health-damaging behaviors are also discussed. The need for additional research that identifies correlations among physiological, social, and behavioral factors and health behaviors, as well as underlying mechanisms, is called for.

Social and personal factors in marijuana use and intentions to use drugs among inner city minority youth.

Limited information is available about the etiology of illicit drug use among minority youth. This study examined predictors of marijuana use and intentions to use marijuana, cocaine/crack, and other drugs for African-American and Hispanic seventh graders (N = 757). Self-reports of marijuana use and intentions to use drugs were collected along with data concerning background, social environmental, and individual characteristics hypothesized to be related to drug use. Results indicated that social influences, including adults, friends, and the most admired person's marijuana use, predicted marijuana use. Individual characteristics, such as a lack of knowledge about the prevalence and negative social consequences of marijuana use, positive attitudes toward marijuana use, and inadequate social, communication, and refusal skills increased suspectability to marijuana use. Lack of self-efficacy was related to intentions to use cocaine and other drugs. Implications of these findings are discussed with respect to the development of effective prevention programs.