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PubMed2003

Gender awareness among physicians--the effect of specialty and gender. A study of teachers at a Swedish medical school.

BACKGROUND: An important goal for medical education today is professional development including gender equality and awareness of gender issues. Are medical teachers prepared for this task? We investigated gender awareness among physician teachers, expressed as their attitudes towards the role of gender in professional relationships, and how it varied with physician gender and specialty. We discuss how this might be related to the gender climate and sex segregation in different specialties. METHOD: Questionnaires were sent to all 468 specialists in the clinical departments and in family medicine, who were engaged in educating medical students at a Swedish university. They were asked to rate, on visual analogue scales, the importance of physician and patient gender in consultation, of preceptor and student gender in clinical tutoring and of physician gender in other professional encounters. Differences between family physicians, surgical, and non-surgical hospital doctors, and between women and men were estimated by chi-2 tests and multivariate logistic regression analyses. RESULTS: The response rate was 65 %. There were differences between specialty groups in all investigated areas mainly due to disparities among men. The odds for a male family physician to assess gender important were three times higher, and for a male non-surgical doctor two times higher when compared to a male surgical doctor. Female teachers assessed gender important to a higher degree than men. Among women there were no significant differences between specialty groups. CONCLUSIONS: There was an interaction between physician teachers' gender and specialty as to whether they identified gender as important in professional relationships. Male physicians, especially from the surgical group, assessed gender important to a significantly lower degree than female physicians. Physicians' degree of gender awareness may, as one of many factors, affect working climate and the distribution of women and men in different specialties. Therefore, to improve working climate and reduce segregation we suggest efforts to increase gender awareness among physicians, for example educational programs where continuous reflections about gender attitudes are encouraged.

Education, Medical↗

PubMed2003

Gender in medicine - an issue for women only? A survey of physician teachers' gender attitudes.

BACKGROUND: During the last decades research has disclosed gender differences and gender bias in different fields of academic and clinical medicine. Consequently, a gender perspective has been asked for in medical curricula and medical education. However, in reports about implementation attempts, difficulties and reluctance have been described. Since teachers are key persons when introducing new issues we surveyed physician teachers' attitudes towards the importance of gender in professional relations. We also analyzed if gender of the physician is related to these attitudes. METHOD: Questionnaires were sent to all 468 senior physicians (29 % women), at the clinical departments and in family medicine, engaged in educating medical students at a Swedish university. They were asked to rate, on five visual analogue scales, the importance of physician and patient gender in consultation, of physician and student gender in clinical tutoring, and of physician gender in other professional encounters. Differences between women and men were estimated by chi-2 tests and multivariate logistic regression analyses. RESULTS: The response rate was 65 %. The physicians rated gender more important in consultation than in clinical tutoring. There were significant differences between women and men in all investigated areas also when adjusting for speciality, age, academic degree and years in the profession. A higher proportion of women than men assessed gender as important in professional relationships. Those who assessed very low were all men while both men and women were represented among those with high ratings. CONCLUSIONS: To implement a gender perspective in medical education it is necessary that both male and female teachers participate and embrace gender aspects as important. To facilitate implementation and to convince those who are indifferent, this study indicates that special efforts are needed to motivate men. We suggest that men with an interest in gender issues should be involved in this work. Further research is needed to find out how such male-oriented endeavours should be outlined.

Journal Article↗

PubMed2004

Exposure-response relationships and drug interactions of sirolimus.

Sirolimus (rapamycin, RAPAMUNE, RAPA) is an immunosuppressive agent used for the prophylaxis of renal allograft rejection and exhibits an immunosuppressive mechanism that is distinct from that for cyclosporine and tacrolimus. The purpose of this manuscript is to discuss the exposure-response relationships and drug interactions of sirolimus. The various factors affecting sirolimus whole blood exposure included first-pass extraction, formulation, food, demographics, liver disease, assay method, and interacting drugs. Clinically significant effects caused by food, pediatric age, hepatic impairment, and interacting drugs require recommendations for the safe and efficacious use of sirolimus in renal allograft patients. An exposure-response model based on multivariate logistic regression was developed using the interstudy data from 1832 renal allograft patients. The analysis revealed an increased probability of acute rejection for sirolimus troughs <5 ng/mL, cyclosporine troughs <150 ng/mL, human leukocyte antigen (HLA) mismatches > or =4, and females. The outcomes suggested that individualization of sirolimus doses immediately after transplantation, based on HLA mismatch and sex, would likely decrease the probability of acute rejections in renal allograft recipients who receive concomitant sirolimus, cyclosporine (full-dose), and corticosteroid therapy. Sirolimus is a substrate for both Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) and undergoes extensive first-pass extraction. Drugs that are known to inhibit or induce these proteins may potentially affect sirolimus whole blood exposure. In healthy volunteers, cyclosporine, diltiazem, erythromycin, ketoconazole, and verapamil significantly increased sirolimus whole blood exposure, and rifampin significantly decreased sirolimus exposure. However, sirolimus whole blood exposure was not affected by acyclovir, atorvastatin, digoxin, ethinyl estradiol/norgestrel, glyburide, nifedipine, or tacrolimus. Among the 15 drugs studied, sirolimus significantly increased the exposures of only erythromycin and S-(-)verapamil.

Adult↗

PubMed2006

Demographic variables affecting patient referrals from general practice dentists to periodontists.

BACKGROUND: Within dentistry, a limited body of literature exists regarding the referral relationships between general practitioners (GPs) and specialists. The purpose of this study was to investigate the referral relationship between GPs and periodontists within the state of Virginia. METHODS: A survey was developed that focused on the demographic variables in the referral relationship between GPs and periodontists. The survey was mailed to 800 dentists throughout the state of Virginia. Descriptive statistics were completed along with multivariate logistic regression analysis comparing the responses with the number of patients referred per month to periodontists. RESULTS: Female respondents were more likely to refer three or more patients per month to a periodontist than a male respondent (P<0.02). Those dentists who practiced with one other dentist were twice as likely to refer more frequently when compared to solo practitioners or larger group practices (P<0.03). Dentists employing two hygienists were more likely to refer patients than those with fewer hygienists (P<0.02). Those whose practices were >5 miles from the nearest periodontist were more likely to refer patients compared to dentists geographically closer to a periodontist (P<0.02). No other variables had a significant effect on the referral of more patients per month to a periodontist. CONCLUSIONS: This study indicates that four demographic variables have a statistical influence on the number of referrals per month from a GP to a periodontist. These variables are as follows: female gender, practicing with one other dentist, employing two or more hygienists, and being >5 miles away from the nearest periodontist.

Adult↗

PubMed2026

Coagulation activation is associated with genomic-instability-related features in TP53-mutated AML and MDS: routine laboratory patterns beyond classical disseminated intravascular coagulation.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of acute myeloid leukemia (AML) associated with poor prognosis. In TP53-mutated AML and myelodysplastic syndrome (MDS), however, the classical ISTH criteria rarely identify overt DIC, although bleeding and thrombotic complications are well documented in acute leukaemia. We hypothesized that these patients exhibit a lower-grade, subclinical coagulation activation that is associated with the underlying genomic-instability-related features of TP53-mutant disease. METHODS: We retrospectively analyzed 107 consecutive patients with TP53-mutated AML (n = 52) or high-risk MDS (MDS, n = 55), median age 65 years, diagnosed and initially evaluated at our centre between 2018 and 2025. Seven routine coagulation markers and 46 co-mutated genes were evaluated for associations with overall survival (OS) using univariate and multivariable Cox regression, continuous dose-response modeling, and unsupervised k-means clustering. Internal validity was assessed by 1000 bootstrap resamples. RESULTS: Overt DIC according to ISTH criteria was rare (15%). Subclinical activation was common: 50% of patients had a D-dimer ≥1 μg/mL, 41% a fibrinogen ≥4 g/L, and 29% an INR ≥1.2. In univariate analysis, D-dimer, fibrinogen, INR, prothrombin time, and activated partial thromboplastin time were each associated with OS (HR 1.33-1.38 per SD; all p < 0.05). Complex karyotype correlated with higher D-dimer (median 1.39 vs. 0.60 μg/mL, p = 0.022) and fibrinogen (3.91 vs. 2.53 g/L, p = 0.007), while TP53 variant allele frequency (VAF) showed modest positive correlations with D-dimer (ρ = 0.21), INR (ρ = 0.27), and PT (ρ = 0.27; all p < 0.05). Clustering identified three coagulation phenotypes: Silent (51%), Thrombo-inflammatory (31%), and Consumption-like (18%), showing a graded but statistically non-significant gradient in molecular features and a stepwise decline in median OS (14, 10 and 8 months; log-rank p = 0.041). After adjustment for complex karyotype, TP53 VAF, and favorable co-mutation count, the Consumption-like phenotype was associated with a non-significant increased risk (HR 1.83, 95% CI 0.92-3.65, p = 0.084), whereas favorable co-mutation pathways remained independently protective (HR 0.56, 95% CI 0.35-0.90, p = 0.016). CONCLUSION: In TP53-mutated AML/MDS, coagulation activation intensity is associated with the degree of genomic instability. The three phenotypes may add biological resolution beyond classical DIC and cytogenetic risk groups, but represent laboratory patterns rather than validated bleeding or thrombosis prediction tools. However, after accounting for genomic features, phenotypes were not independent predictors of outcome, with complex karyotype, TP53 VAF, and favorable co-mutation count driving prognosis. Because treatment intensity and other clinical confounders were not available, these survival associations are hypothesis-generating. Coagulation profiling remains inexpensive, widely accessible, and offers a practical window into disease biology that warrants prospective validation.

TP53↗

PubMed1999

Patient factors related to the odds of receiving prevention services in Veterans Health Administration medical centers.

OBJECTIVE: To examine the association between patient characteristics and the odds of receiving 13 health promotion/disease prevention services recommended by the US Preventive Services Task Force (USPSTF) for average-risk individuals. METHODS: A mail survey was sent to a random sample of 68,422 veterans who obtained primary care from any of the 153 Veterans Health Administration facilities in 1996; 44,304 responded (adjusted response rate was 68%). Multivariate logistic regression models were used. RESULTS: Demographic factors, health risk behaviors, and self-reported health were associated with the odds of receiving prevention services. Current smokers, heavy alcohol drinkers, and females were less likely to receive many health promotion services, whereas regular exercisers, overweight individuals, males, those reporting poorer health, individuals reporting high or controlled blood pressure, and those reporting high or controlled cholesterol levels were more likely to receive USPSTF-recommended prevention services. CONCLUSION: Substantial proportions of veterans were likely to obtain prevention services recommended by the USPSTF for average-risk individuals. Nevertheless, veterans who reported being current smokers, heavy drinkers, or female were less likely to obtain these services. These subgroups may benefit from additional initiatives.

Adult↗

PubMed2005

Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After 1 Year.

Context: Athletes in the United States are at high risk for using spit (smokeless) tobacco (ST) and incurring its associated adverse health effects.Objective: To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes.Design: Stratified, cluster-randomized controlled trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated, as did 48 certified athletic trainers.Intervention(s): For college athletic trainers and associated dental professionals, a 3-hour video conference, and for collegiate athletes, an oral cancer screening with feedback and brief counseling during the preseason health screenings, athletic trainer support for cessation, and a peer-led educational baseball team meeting.Main Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report. At the end of the study, the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment. We used multivariable logistic regression models for clustered responses (generalized estimating equations) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use.Results: Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and 8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95% confidence interval = 0.35-0.99). Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence interval = 1.40- 2.82) and athletic trainers' report that the baseball coach supported ST-use prevention activities (odds ratio = 1.43, 95% confidence interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively high in both groups (36%), we noted no significant difference between the groups (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group. The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges, other anti-tobacco activity in control colleges, and/or the small sample of dependent ST users enrolled in the study.

Journal Article↗

PubMed1986

Predictive model for prognosis in advanced diffuse histiocytic lymphoma.

The purpose of this study was to examine the validity of a predictive model for response to treatment and survival in advanced diffuse histiocytic lymphoma. One hundred twenty-seven consecutive patients with Ann Arbor stage II-IV diffuse histiocytic lymphoma, who completed treatment between 1974 and 1984 in one of four different Memorial Hospital combination chemotherapy protocols, were reviewed. The median follow-up time was 66.9 months for survivors (range, 21-153.1 months). Factors studied included: age; sex; Ann Arbor stage; prior therapy; B symptoms; serum lactic dehydrogenase (LDH); sites of initial disease; and tumor bulk. LDH was grouped accordingly (units/liter): low, less than 225; medium, 225-500; high, greater than 500. Each patient was assigned an overall level of site involvement (LSI) from the following mutually exclusive groups: group I, peripheral lymph node (PLN) (including +/- Waldeyer ring involvement, +/- spleen); group II, extranodal disease (EN) +/- PLN; group III, retroperitoneal lymph node (RLN) +/- PLN; group IV, bulky mediastinal disease (MED) +/- any other disease; group V, EN with RLN +/- PLN. The Ann Arbor staging system failed to dissect patient groups differing significantly in their prognosis. Serum LDH, LSI, and age were the only factors important for predicting response and survival after multivariate logistic regression and a parametric Weibull survival analysis. Using three levels of serum LDH and correlating them with the different LSI, four tentative "stages" differing significantly in their survival at 48 months were defined: stage I, low LDH, any LSI (80% alive); stage II, medium LDH, PLN, and/or EN (50% alive); stage III, high LDH, PLN, and/or EN or medium LDH, RLN +/- PLN +/- EN, and/or MED (35% alive); stage IV, high LDH, RLN +/- PLN +/- EN, and/or MED (15% alive). Identification of prognostic stages on the basis of LDH level and LSI will allow more accurate comparison of clinical trials for patients with advanced diffuse histiocytic lymphoma.

Adult↗

PubMed2005

Pretreatment serum hemoglobin level as a predictive factor of response to neoadjuvant chemotherapy in patients with locally advanced squamous cervical carcinoma: a preliminary report.

OBJECTIVE: The aim of this study was to evaluate the predictive value of pretreatment serum hemoglobin level (Hb) together with a series of clinical and pathological variables available before neoadjuvant chemotherapy in locally advanced squamous cervical cancer. METHODS: The influence on response to neoadjuvant chemotherapy of a series of pretreatment clinico-pathological features: hemoglobin level at diagnosis, age, parity, menopausal status, body mass index, clinical stage, tumor diameter, and nuclear grading were analyzed on 73 patients with locally advanced cervical cancer treated with platinum-based neoadjuvant chemotherapy followed by radical surgery. The relationships between pretreatment variables and response to chemotherapy were assessed in univariate and multivariate settings. A univariate and multivariate logistic regression model was adapted to predict an "optimal" response (pathological complete response or more than 50% reduction in tumoral diameter) or "sub-optimal" response (<50% reduction in tumoral diameter). RESULTS: Seventy-three patients-clinical stage: Ib2: 29 (39.7%) IIa: 22 (30.1%) IIb: 22 (30.1%)-received 3 cycles of platinum-based neoadjuvant chemotherapy followed by type III radical hysterectomy. A complete response to neoadjuvant chemotherapy was significantly associated with higher level of pretreatment hemoglobin (mean 14.0 mg/dl) compared to patients with > or =50% response (12.7 mg/dl) or <50% (11.9 mg/dl) (P = 0.002). At multivariate analysis, Hb level was found to be the most powerful and significantly related factor to response to neoadjuvant chemotherapy. A hemoglobin threshold of 12 mg/dl was able to distinguish between patients-with > or =12 mg/dl-at higher probability to respond to neoadjuvant chemotherapy from the ones at lower probability (hemoglobin level under 12 mg/dl). Patients with a complete response to chemotherapy had a 100% survival compared to 93.1% and 53.8% for patients with responses > or =50% and <50% respectively (P = 0.0001). Patients with a pretreatment hemoglobin level of > or =12 mg/dl showed a survival of 87% compared to 63% for patients with a lower hemoglobin level (P = 0.008). CONCLUSIONS: Pretreatment Hb level showed a prognostic and independent predictive value for response to neoadjuvant chemotherapy in locally advanced cervical cancer. In our preliminary report, performed on a limited sample, a threshold of 12 mg/dl seems to be helpful to distinguish between "optimal" and "non-optimal" response.

Analysis of Variance↗

PubMed1997

Predicting the outcome of surgical treatment of vulvar vestibulitis.

OBJECTIVE: To identify predictive factors for success or failure of perineoplasty for severe vulvar vestibulitis. METHODS: Seventy-nine women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992-1994. Sixty (76%) who experienced a complete response were compared with 19 (24%) who had an incomplete response. Using univariate and then multivariate (logistic regression) analysis, the two groups were compared with regard to preoperative demographic, social, and medical variables, as well as physical findings in the vestibule. RESULTS: The complete- and incomplete-response groups were similar in all comparisons except for constant vulvar pain of vestibular origin (in addition to dyspareunia) and the presence of symptoms since first coitus. On multiple logistic regression, these characteristics had odds ratios (and 95% confidence intervals) of 4.97 (1.49, 16.63) and 5.83 (1.74, 19.55), respectively. CONCLUSION: An incomplete response to perineoplasty may be anticipated in women with vulvar vestibulitis associated with dyspareunia since their first episode of intercourse and in those with associated persistent vulvar pain. Treatment approaches other than surgery should be considered for such patients.

Adolescent↗

PubMed1999

Bivariate logistic regression: modelling the association of small for gestational age births in twin gestations.

Clustered binary responses, such as disease status in twins, frequently arise in perinatal health and other epidemiologic applications. The scientific objective involves modelling both the marginal mean responses, such as the probability of disease, and the within-cluster association of the multivariate responses. In this regard, bivariate logistic regression is a useful procedure with advantages that include (i) a single maximization of the joint probability distribution of the bivariate binary responses, and (ii) modelling the odds ratio describing the pairwise association between the two binary responses in relation to several covariates. In addition, since the form of the joint distribution of the bivariate binary responses is assumed known, parameters for the regression model can be estimated by the method of maximum likelihood. Hence, statistical inferences may be based on likelihood ratio tests and profile likelihood confidence intervals. We apply bivariate logistic regression to a perinatal database comprising 924 twin foetuses resulting from 462 pregnancies to model obstetric and clinical risk factors for the association of small for gestational age births in twin gestations.

Adolescent↗

PubMed2006

Self-reported adherence in patients with asthma.

BACKGROUND: Not all patients with asthma adhere to their prescribed drug regimens. The Behavioral Model of Health Services Utilization, organized as predisposing, enabling, and need variables, may be useful in identifying variables related to adherent medication-taking behavior. OBJECTIVE: To examine the relationship between predisposing, enabling, and need variables and self-reported adherence with asthma controller drugs. METHODS: A secondary analysis was conducted from a cross-sectional study using survey and claims data obtained from adults with asthma enrolled in a managed care organization. Independent variables included predisposing (age, gender, race, years with asthma, number of comorbidities, health beliefs), enabling (income, number of metered-dose inhaler [MDI] instructors, inhaler technique, perceived physician access), and need (patient-perceived severity, symptom-derived severity, health-related quality of life). Adherence was measured using a 4 item questionnaire scored as the mean of the responses, with 5 denoting highest adherence. Multivariate regression analysis was used to identify variables with statistically significant relationships to self-reported adherence. Stepwise backward elimination was used, with the final model consisting of variables considered significant at p less than 0.05. RESULTS: The 573 respondents (1270 packets sent; 45% response rate) were primarily white (89.5%) and female (71.0%), with an average age of 40.5 +/- 12.4 years (mean +/- SD) and average asthma duration of 18.3 +/- 14.2 years. The mean adherence scale score was 3.7 +/- 1.1, with 84.6% indicating some level of nonadherence (score <5). The final model had an adjusted R(2) of 0.26 and included 6 independent variables. Better adherence was associated with stronger beliefs in the benefits of treatment and trigger avoidance, greater perceived asthma severity, longer asthma duration, more MDI instructors, and higher scores on the Short-Form 36 mental component summary. CONCLUSIONS: Complex beliefs, perceptions, and experiences constitute the variables associated with adherent medication-taking behavior. Future longitudinal studies should include these variables to determine the predictive strength of the model.

Adolescent↗

PubMed1990

[Prognostic factors affecting survival and response in patients with advanced non-small cell lung cancer treated with combination chemotherapy].

One-hundred and ninety-nine patients who had an inoperable stage III or IV non-small cell lung cancer (NSCLC) and collected were analyzed on the basis of factors affecting survival duration and response to chemotherapy. These patients were registered into a prospective randomized trial conducted from May of 1986 to April of 1988, and received either cisplatin and vindesine, cisplatin, vindesine and mitomycin C, or cisplatin and etoposide alternating with vindesine and mitomycin C. In the univariate analysis, sex, ECOG's performance status (PS), weight loss within previous 6 months, clinical stage, serum albumin value, serum lactate dehydrogenase level and hemoglobin (Hb) level were considered to be significant factors for survival (p less than 0.05). In the multivariable analysis using Cox's proportional model, clinical stage, PS, sex, weight loss and Hb level were proven to be significant variables for survival in the order of importance. When the response to chemotherapy was included in a conditional multivariable analysis, it was strongly associated with survival duration. A multivariable analysis of response using the logistic regression method demonstrated that female sex, cisplatin, vindesine and mitomycin combination regimen, squamous cell type, and no weight loss were significantly predictive of response outcome. These results are useful when comparing the response data and survival of completed studies and designing future trials in advanced NSCLC.

Adult↗

PubMed2006

Potential predictors of chemotherapy response in ovarian cancer--how do we define chemosensitivity?

OBJECTIVE: The aim of this study was to assess whether microvessel density (measured by CD31), vascular endothelial growth factor (VEGF) or multidrug resistance (MDR1) could determine the response to chemotherapy or act as prognostic factors in ovarian cancer. METHODS: Seventy-nine ovarian specimens were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for univariate analysis. Kaplan Meier survival curves were used, log-rank was used for univariate analysis and a Cox proportional hazards regression model was used for multivariate evaluation. Response to chemotherapy was assessed after 6 months and again after 1 year. RESULT: Quantifying VEGF proved to be a valuable independent prognostic indicator in progression-free survival (PFS) (p<0.05) and overall survival (OS) (p<0.0001). VEGF correlated with response to chemotherapy at the 6-month interval (r=0.446, p<0.001) but failed to correlate at the 1-year interval. Increased staining with CD31 was associated with decreased PFS (p<0.01) and OS (p<0.01) in univariate but not multivariate analysis. MDR1 failed to act as a prognostic marker or as a predictor of response to chemotherapy. CONCLUSION: VEGF correlates with response to chemotherapy at the 6-month but not the 12-month interval. What should our criteria be for determining sensitivity to chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but other factors are likely to be involved and perhaps molecular profiling will determine which factors will be important for determining the response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register.

BACKGROUND: Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted. OBJECTIVE: To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA. METHODS: The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression. RESULTS: 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission. CONCLUSIONS: These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.

Adult↗

PubMedDate not supplied

Predictors of the response to tricyclic antidepressants in major depression.

In a relatively young sample of 108 nonbipolar patients with major depressive disorder and at least moderately severe depression, the contribution of a comprehensive set of socio-demographic, psychosocial, clinical and personality trait variables toward the prediction of short-term, multidimensionally evaluated response to tricyclic antidepressants was investigated by univariate and multivariate analyses. There is a naturalistic study without a standard treatment protocol, but treatment type, duration and dosage were controlled. Only patients who received at least moderate dosages of tricyclic antidepressants for minimum four weeks were included in this study. A relatively low number of predictors emerged. Initial severity of both symptoms and impairment of functioning were the most powerful predictors for all outcome criteria. Illness history was also relevant. Personality traits reflecting vulnerable personality style at the emotional and interpersonal level proved their predictive value. The combination of independent variables by multivariate regression analyses improve the prediction of treatment response.

Adolescent↗

PubMed1998

Ergonomic stressors and upper extremity disorders in vehicle manufacturing: cross sectional exposure-response trends.

OBJECTIVE: To evaluate the association between upper extremity soft tissue disorders and exposure to preventable ergonomic stressors in vehicle manufacturing operations. METHODS: A cross sectional study was conducted in one vehicle stamping plant and one engine assembly plant. A standardised physical examination of the upper extremities was performed on all subjects. An interviewer administered questionnaire obtained data on demographics, work history, musculoskeletal symptoms, non-occupational covariates, and psycho-physical (relative intensity) ratings of ergonomic stressors. The primary exposure score was computed by summing the responses to the psychophysical exposure items. Multivariate regression analysis was used to model the prevalence of disorders of the shoulders or upper arms, wrists or hands, and all upper extremity regions (each defined both by symptoms and by physical examination plus symptoms) as a function of exposure quartile. RESULTS: A total of 1315 workers (85% of the target population) was examined. The prevalence of symptom disorders was 22% for the wrists or hands and 15% for the shoulders or upper arms; cases defined on the basis of a physical examination were about 80% as frequent. Disorders of the upper extremities, shoulders, and wrists or hands all increased markedly with exposure score, after adjustment for plant, acute injury, sex, body mass index, systemic disease, and seniority. CONCLUSIONS: Musculoskeletal disorders of the upper extremities were strongly associated with exposure to combined ergonomic stressors. The exposure-response trend was very similar for symptom cases and for physical examination cases. It is important to evaluate all dimensions of ergonomic exposure in epidemiological studies, as exposures often occur in combination in actual workplaces.

Adult↗

PubMed2000

Stepwise multimodal approach in the treatment of Kasabach-Merritt syndrome.

BACKGROUND: The purpose of the present study was to evalutate the various treatment modalities for Kasabach-Merritt syndrome (KMS) and to identify the most reliable treatment modalities. METHODS: A retrospective analysis was performed on 37 KMS patients who were admitted to Seoul National University Hospital between January 1979 and June 1999. Age, sex, locations of the hemangiomas, clinical symptoms and hematologic data were analyzed by multivariate logistical regression analysis to determine the response to various treatment modalities. RESULTS: Twenty-four of 37 patients (20 boys and 17 girls) were diagnosed during infancy. The locations of hemangioma were superficial skin in 31 patients, combined skin and visceral organs in four patients and visceral organs only in two patients. Tumor size was more than 5 cm in diameter in all cases, except for one. The treatment principle of KMS in our center involves a stepwise multimodal approach. Of the 37 cases, surgical resection was performed in two. Steroids were tried initially in 35 patients over a 1 week period, with an initial response rate of 11.4% (4/35). Combined steroid/radiation treatment was given in 28 cases, with a response rate of 75.0% (21/28). Four of five patients with additional interferon (IFN)-alpha therapy improved. No significant correlations were found between the prognostic factors, such as age, sex, size and locations of the hemangioma, hematologic data and the treatment modalities. CONCLUSIONS: Based on the experiences in a single center over a period of 20 years, we recommend a stepwise multimodal approach for the treatment of KMS; for example, steroid, radiation therapy and IFN-alpha in this order. However, surgical treatment is helpful if total resection is possible.

Abnormalities, Multiple↗