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Results for “Multivariate response regression”

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PubMed2005

Internal consistency reliability is a poor predictor of responsiveness.

BACKGROUND: Whether responsiveness represents a measurement property of health-related quality of life (HRQL) instruments that is distinct from reliability and validity is an issue of debate. We addressed the claims of a recent study, which suggested that investigators could rely on internal consistency to reflect instrument responsiveness. METHODS: 516 patients with chronic obstructive pulmonary disease or knee injury participating in four longitudinal studies completed generic and disease-specific HRQL questionnaires before and after an intervention that impacted on HRQL. We used Pearson correlation coefficients and linear regression to assess the relationship between internal consistency reliability (expressed as Cronbach's alpha), instrument type (generic and disease-specific) and responsiveness (expressed as the standardised response mean, SRM). RESULTS: Mean Cronbach's alpha was 0.83 (SD 0.08) and mean SRM was 0.59 (SD 0.33). The correlation between Cronbach's alpha and SRMs was 0.10 (95% CI -0.12 to 0.32) across all studies. Cronbach's alpha alone did not explain variability in SRMs (p = 0.59, r2 = 0.01) whereas the type of instrument was a strong predictor of the SRM (p = 0.012, r2 = 0.37). In multivariable models applied to individual studies Cronbach's alpha consistently failed to predict SRMs (regression coefficients between -0.45 and 1.58, p-values between 0.15 and 0.98) whereas the type of instrument did predict SRMs (regression coefficients between -0.25 to -0.59, p-values between <0.01 and 0.05). CONCLUSION: Investigators must look to data other than internal consistency reliability to select a responsive instrument for use as an outcome in clinical trials.

Clinical Trials as Topic↗

PubMedDate not supplied

Pediatrician practices regarding referral to early intervention services: is an established diagnosis important?

OBJECTIVE: Early intervention (EI) programs provide services to children with developmental conditions, regardless of whether such children have an underlying medical diagnosis. We aim to (1) Determine the proportion of general pediatricians who believe an established diagnosis is important when considering EI referral; and (2) Determine whether this perception is associated with lower reported likelihood of referral. METHODS: Mailed survey to random sample of pediatricians. We used multivariable logistic regression to study the association between the perception that a medical diagnosis is important when referring to EI, and the reported likelihood of EI referral for children with common developmental conditions. RESULTS: Response rate was 55% (894 of 1617). A total of 64% of respondents considered an established diagnosis important for EI referral. Likelihood of referral for delayed speech was lower among those who considered a diagnosis important than among those who did not (77% vs 87%; P = .02). Similar patterns held for global delay (91% vs 97%; P = .02), loss of developmental milestones (80% vs 88%; P = .03), and parental concern for inappropriate development (45% vs 60%; P = .002). In multivariable models, perception of the importance of an established diagnosis was associated with lower likelihood of referral for children with delayed speech (adjusted odds ratio [aOR] 0.48; 95% confidence interval [CI] 0.26-0.87) and for parental concern for inappropriate development (aOR 0.46; 95% CI 0.30-0.72). CONCLUSIONS: A majority of general pediatricians believe that an established diagnosis is important when considering EI referral. This perception is associated with decreased reported referral for children with speech delay and those whose parents express concern for inappropriate development.

Attitude of Health Personnel↗

PubMed2005

A pilot case-control study of gamma-radiation sensitivity and risk of papillary thyroid cancer.

In vitro gamma-radiation-induced chromatid breaks per cell (b/c) in lymphocytes may be associated with risk of papillary thyroid cancer (PTC). This pilot case-control study involved 106 patients with thyroid disease (57 with PTC and 49 with benign thyroid disease) and 105 cancer-free matched controls. Multivariate logistic regression analyses identified that an elevated gamma-radiation-induced b/c value was a risk factor for PTC (adjusted odds ratio = 4.54; 95% CI, 2.07-9.95), and a dose-response relationship was evident when the b/c values were categorized into tertiles. High levels of chromatid breaks induced by gamma-radiation may constitute an independent risk factor for PTC, but further study is needed.

Adolescent↗

PubMed1987

Predicting the pharmacodynamics of heparin: a clinical evaluation of the Hepcon System 4.

The magnitude of the anticoagulation response to heparin (heparin responsiveness) varies substantially from patient to patient. Identifying extremes of sensitivity and resistance prior to intravenous administration of heparin would facilitate anticoagulation for cardiopulmonary bypass (CPB). The performance of the Hepcon System 4 (HemoTec, Inc, Englewood, CO), an instrument designed for that purpose, was tested. Using nonheparinized blood samples from 157 patients scheduled for surgery requiring CPB, this device performed activated coagulation times (ACT) with three different concentrations of in vitro heparin. After determining each patient's in vitro heparin response, the heparin dose predicted to produce ACT values of 480 seconds (group 1, N = 77) or 600 seconds (group 2, N = 80) was administered. Five minutes later each patient's ACT was determined with the Hemochron method (International Technidyne, Inc, Edison, NJ). Simultaneously, several other variables that might predict heparin responsiveness were investigated. When compared with the observed ACT, the Hepcon System 4 inadequately predicted the response. There was considerable scatter in this comparison, but most frequently the in vitro method substantially underestimated the in vivo heparin dose requirement. Heparin responsiveness decreased significantly with high platelet counts and advanced age, but was unaffected by the initial hematocrit, ACT, partial thromboplastin time, or preoperative heparin therapy. Previous investigations have not identified a relationship between advanced age and reduced heparin responsiveness. Combining the Hepcon heparin dose-response in vitro method with the other parameters evaluated, stepwise regression could only account for 39% of the observed variability in heparin responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1998

[Prognostic factors in low-grade lymphoma].

PURPOSE: Prognostic factors in low grade non-Hodgkin's lymphoma (LGL) are not well established. The aim of this study is to investigate prognostic factors on LGL treated in our institution during the last decade. PATIENTS AND METHODS: The study was carried out on 70 cases of newly diagnosed LGL, most treated with CVP or clorambucil and prednisone. The median follow-up was 37 months (1-132). Variables reported as prognostic factors in previous series were subjected to bivariate and multivariate analysis. RESULTS: Relevant clinical features were: Ann Arbor III-IV stage 74%, ECOG > or = 2-17%, bone marrow involvement 60% and large tumor burden according to MD Anderson criteria 21%. Complete response (CR) was achieved in 50% and partial response in 29%. In bivariate analysis factors related with poor CR were B symptoms, large tumor burden, high LDH and more than one extranodal site involvement. Logistic regression showed that large tumor burden (p = 0.02; OR = 0.07) and B symptoms (p = 0.07; OR = 0.14) were the best prognostic factors of poor CR. Five year global survival (GS) was 55%, with a median of 76 months. In univariate analysis factors related with GS were ECOG > or = 2, B symptoms, bulky, large tumor burden, retroperitoneo involvement and absence of CR. In multivariate analysis the only factor related with poor GS was large tumor burden (p < 0.00001; RR = 5.93). When therapeutic response was included in the model, absence of CR (p = 0.008; RR = 3.40) and large tumour burden (p = 0.005; RR = 3.86) were the factors selected. CONCLUSIONS: In LGL tumor burden was the most important prognostic variable. Tumor response showed less importance than in high grade lymphomas.

Adult↗

PubMed1994

Salvage therapy for multiple myeloma: the University of Arkansas experience.

OBJECTIVE: To summarize a spectrum of salvage regimens for multiple myeloma (MM) developed during the past decade. DESIGN: We reviewed the experience at the University of Arkansas in the management of patients with MM who failed to achieve remission ("primary unresponsive") or had a relapse despite myelosuppressive doses of chemotherapy ("resistant relapse"). MATERIAL AND METHODS: Results with use of the various chemotherapeutic protocols are presented, and multivariate regression analysis was applied to determine the independent contributions of certain factors toward event-free and overall survival. RESULTS: The VAD regimen (vincristine sulfate, Adriamycin [doxorubicin hydrochloride], and dexamethasone) yielded responses in 29% of previously unresponsive and 46% of relapsed cases of MM, in comparison with 25% and 21%, respectively, with use of dexamethasone only. Responses occurred more frequently when tumor cell RNA content was high, tumor burden was low, and duration of drug resistance was less than 1 year. The duration of survival in patients who received high doses of melphalan was decreased in those with increased serum levels of lactate dehydrogenase. EDAP (etoposide, dexamethasone, ara-C, and cisplatin) produced 75% or more tumor cytoreduction in 8 of 20 patients. Overall in patients with an increasing number of adverse factors, response rates and survival decreased progressively with less intensive therapy but were unaffected when more intensive therapy was used. In the multivariate analysis, the most important features for extended survival were a low beta 2-microglobulin level before transplantation and application of two bone marrow transplants within 6 months. CONCLUSION: Variables relative to the patient's overall medical condition, prior treatment, characteristics of MM at diagnosis, and response history should be carefully assessed to determine a plan for salvage therapy that will maximize the opportunity for sustained remission and survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Classification and prognostic evaluation in multiple myeloma. A retrospective study of relationship of survivals and responses to chemotherapy to immunological types, 20 single prognostic factors, 15 clinical staging systems, and 6 morphological classifications.

In a group of 136 completely followed up patients with multiple myeloma, the prognostic significance of the immunological myeloma types, of 20 different single prognostic factors, of 15 clinical staging systems, and of 6 morphological classifications was retrospectively investigated by means of the calculation of mean survivals, survival curves, and responses to chemotherapy. A univariate analysis was employed in order to correlate each prognostic parameter at presentation with the survival in the whole group; a multivariate analysis according to the Cox's hazards regression model was used in order to select the most powerful prognostic variables. The patients were grouped according to the myeloma immunological types, to the mean value of each single prognostic factor, and to each stage of the clinical and morphological systems. Causes of death were also related to immunological multiple myeloma types. All single variables, except age and serum calcium, presented a significant relationship with the survival, even if at different significance levels. Cox's regression model selected among them, serum levels of beta 2-microglobulin, percentage of bone marrow plasma cells, hemoglobinemia, lytic bone lesions, and Bence-Jones proteinuria as the most significant factors related to survival. Each clinical and morphological staging system divided groups of patients with significant differences in mean survivals, or in survival curves, or in response to therapy. Multiple myeloma type IgA and micromolecular, with Bence-Jones proteinuria, and type lambda were associated with a poor prognosis, with low therapeutical response, and with the development of fatal renal failure. All these parameters, together with new prognostic factors, are useful in the prognostic evaluation, and, when applied in different steps of the diagnosis and the therapy, allow of studying the clinical course of multiple myeloma under different perspectives, in order to have a more complete picture of the disease and of the single patient.

Adult↗

PubMed2003

Bayesian analysis of a multivariate null intercept errors-in-variables regression model.

Longitudinal data are of great interest in analysis of clinical trials. In many practical situations the covariate can not be measured precisely and a natural alternative model is the errors-in-variables regression models. In this paper we study a null intercept errors-in-variables regression model with a structure of dependency between the response variables within the same group. We apply the model to real data presented in Hadgu and Koch (Hadgu, A., Koch, G. (1999). Application of generalized estimating equations to a dental randomized clinical trial. J. Biopharmaceutical Statistics 9(1):161-178). In that study volunteers with preexisting dental plaque were randomized to two experimental mouth rinses (A and B) or a control mouth rinse with double blinding. The dental plaque index was measured for each subject in the beginning of the study and at two follow-up times, which leads to the presence of an interclass correlation. We propose the use of a Bayesian approach to model a multivariate null intercept errors-in-variables regression model to the longitudinal data. The proposed Bayesian approach accommodates the correlated measurements and incorporates the restriction that the slopes must lie in the (0, 1) interval. A Gibbs sampler is used to perform the computations.

Bayes Theorem↗

PubMed2005

Prediction of early and confirmed virological response by genotypic inhibitory quotients for lopinavir in patients naïve for lopinavir with limited exposure to previous protease inhibitors.

OBJECTIVE: To determine the impact of genotypic inhibitory quotient (GIQ) for lopinavir (LPV) in patients failing HAART with limited antiretroviral exposure. DESIGN: Retrospective analysis of a prospective trial. METHODS: Lopinavir GIQ was calculated as the ratio between the mean trough concentration (C(trough)) and the number of protease mutations using eight different HIV drug resistance mutation lists or algorithms. Early (by week 12) and confirmed (up to week 24) virological response (HIV-RNA< 400 copies/mL, ECVR) was used as dependent variable in logistic regression model. RESULTS: Seventy-one of 109 (65%) patients achieved ECVR. At multivariable logistic regression analysis, each mug/mL increase of GIQ was correlated with increasing probability of ECVR as far as the following mutations were computed: multi-protease inhibitor (PI) associated mutations listed by IAS (OR=1.17; 95% CI=0.99-1.39; P=0.058), mutations associated with LPV resistance by ANRS algorithm (OR=1.21; 95% CI=1.02-1.44; P=0.03), major mutations associated with LPV resistance by Stanford database (OR=1.16; 95% CI=1-1.35; P=0.05), and the whole set of mutations associated with LPV resistance in the same database (OR=1.22; 95% CI=1.02-1.46; P=0.03). Using ROC curve method, a specific threshold GIQ was assessed, above which this parameter could predict ECVR with the highest sensitivity (74.6% with GIQ obtained through Stanford LPV mutations) or specificity (89.5% with GIQ obtained through ANRS LPV mutations). CONCLUSIONS: Our results suggest that increasing GIQ can improve virological outcome even in patients with limited exposure to PIs. Further studies are necessary to understand what HIV protease mutations should be considered and whether such mutations should be weighted differently to improve LPV GIQ predictive value.

Adult↗

PubMed1986

Decision making in prehospital sudden cardiac arrest.

Many studies of prehospital resuscitation report on selected populations. We examined a series of 445 unselected nontraumatic cardiac arrests. Emergency cardiac care (ECC) was not initiated in 126 (28%). ECC was begun in 319 (78%), but was terminated in 132 (33%). Ninety-four (21%) were admitted to the hospital with palpable pulses and organized rhythm (successful resuscitation/save rate for patients presenting in ventricular fibrillation was 50%/25%. Multivariate regression analysis was used to identify the relative importance of significant variables in predicting survival, and the analysis identified the presence of ventricular fibrillation, short paramedic response times, and short paramedic treatment times.

Aged↗

PubMed1996

Factors associated with unrecognized HIV-1 infection in an inner-city emergency department.

STUDY OBJECTIVE: To determine the prevalence of and risk factors associated with unrecognized HIV-1 infection among medical patients presenting to an inner-city emergency department. METHODS: We conducted anonymous HIV-1 testing in subjects interviewed for risk behaviors and knowledge of HIV status at an inner-city ED in the Bronx, New York. Our subjects were consecutive adult medical patients in noncritical condition (N = 1,744) who were evaluated by three physicians providing primary emergency care. Each patient was given a structured interview for demographic characteristics, risk behaviors, and knowledge of HIV status. Excess serum, drawn for clinical purposes, was linked without identifiers to responses and tested for antibodies to HIV-1. In subjects who denied HIV infection, we tested associations with seropositivity using univariate analyses and logistic-regression techniques (multivariate). RESULTS: Of the 1,744 patients interviewed, 656 (37.6%) reported HIV risk behaviors. Of 970 tested for HIV-1 antibodies, 125 (12.9%) were seropositive. The prevalence of HIV-1 infection among those who denied known infection was 4.0% (35 of 875). In the multivariate model, independent predictors of unrecognized HIV-1 infection were age 35 to 44 years, crack cocaine use, history of syphilis, and ED diagnosis of an infection not necessarily related to HIV infection. Unrecognized HIV-1 infection was more likely among patients admitted to the hospital, but 21 of the 35 with unrecognized infection (60%) were not admitted and in 9(25.7%) no risk factors were identified. CONCLUSION: More than one third of patients who visited one inner-city ED acknowledged HIV risk behaviors. One quarter of patients with unrecognized HIV-1 infection reported no identifiable risk factors. Easily accessible HIV counseling and testing should be considered in EDs in areas serving persons at risk for HIV infection.

Adolescent↗

PubMed2006

[Characteristics of risk groups with an insufficient demand for dental services - results of the study of health in Pomerania (SHIP)].

AIM: The purpose of this study was to identify risk groups for low dental care utilisation and to highlight adequate determinants for necessary action. METHODS: The database was the "Study of Health in Pomerania" (SHIP), a cross-sectional sample drawn from the adult population (20 - 79 years) in a northeast region of Germany. 4310 of 7008 randomly selected inhabitants participated in the examinations (response rate 68.8 %). The use of dental care in the last year was analysed using logistic regression according to the conceptual model by Andersen and Newman. RESULTS: Multivariate analysis revealed that participation in the bonus scheme system of the statutory sickness funds (OR = 8.2) and participation in the bonus system of the private health insurance companies (OR = 2.6) as "enabling resources" predicted dental care use in the last year. "Objektive need" (OR = 1.02) is weaker associated with dental care utilisation than "subjective need", for instance the attitude towards need of regular dental checkups. Presence of own teeth is a significant predictor for dental care utilization (OR = 3.3), whereas edentulous persons, those with complete denture prosthesis, don't think about possible oral problems and don't visit the dentist at least once a year. Among "predisposing factors" only gender and education were significant determinats for dental care utilization. CONCLUSIONS: The conclusions concerning the significant influence of subjective need and promotional impact of the bonus scheme are important for health care. Financial incentives and motivation for regular prevention should be continued and upgraded. Measures to improve preventive dental care utilization should focus on persons with low educational levels and on men with inadequate dental care utilisation. The mental anchorage of the term "oral health" rather than the conventional term "dental health" is important, so that edentulous persons become conscious of regular prevention pointers to maintain a high quality of life.

Adult↗

PubMed1995

Randomized controlled trial of recombinant interferon-alpha 2b in the treatment of Chinese patients with chronic hepatitis C.

To evaluate the efficacy of recombinant interferon (IFN) alpha 2b in the treatment of Chinese patients with chronic hepatitis C, a randomized controlled trial was conducted in 50 chronic hepatitis C patients: 25 patients received 3 million units of subcutaneously injected recombinant IFN-alpha 2b three times per week for 6 months, and 25 patients received no specific treatment were used as controls. At the end of the IFN treatment, 19 patients (76%) in the IFN-treated group normalized serum ALT compared with only 6 patients (24%) in the control group (p < 0.01). Relapse within 6 months after the completion of treatment occurred in 13 IFN-treated patients (68%). Normalized serum ALT was seen in 6 patients (24%) in the IFN-treated group and 1 patient (4%) in the control group 6 months after discontinuation of IFN therapy (p = 0.10). The presence of serum hepatitis C virus (HCV) RNA measured by reverse transcription-polymerase chain reaction was detected at the end of the IFN treatment in all 13 patients who relapsed after cessation of therapy. In only 3 of 25 IFN-treated patients (12%) was the presence of serum HCV RNA not detectable at the end of the IFN treatment or 6 months after cessation of therapy. No patient in the control group had undetectable serum HCV RNA during the study period. Using multivariate logistic regression analysis, the low pretreatment levels of HCV RNA, measured by a quantitative branched DNA amplification assay, was the only independent predictor of a sustained response to IFN therapy (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

PubMed2006

Maternal exposure to second-hand tobacco smoke and pregnancy outcome among couples undergoing assisted reproduction.

BACKGROUND: Exposure to second-hand tobacco smoke is preventable, yet common. This study assessed relationships between maternal exposure to second-hand tobacco smoke and adverse pregnancy outcomes. METHODS: We measured cotinine (a biomarker of tobacco smoke) in urine from 921 women undergoing assisted reproductive technologies (ARTs) between 1994 and 1998. We also collected information on self-reported exposure to second-hand smoke at home or at work, in addition to parental smoking during the women's childhood. RESULTS: In crude analysis, creatinine-adjusted cotinine levels were associated with a slight decrease in implantation rate among non-smoking women (11.1% in the lowest cotinine quintile versus 8.2% in the highest cotinine quintile; P=0.13). However, in multivariate logistic regression, cotinine levels above the median were not associated with failed fertilization, failed implantation or spontaneous abortion, nor was there evidence of a dose-response relationship among cotinine quintiles. After excluding women in couples diagnosed with male factor infertility, there were increased odds of having a spontaneous abortion among non-smoking women who reported that both parents smoked while they were children growing up compared with women reporting that neither parent smoked [adjusted odds ratio (OR) = 4.35; 95% confidence interval (CI) = 1.04-18.1]. CONCLUSIONS: Female exposure to second-hand smoke as a child or in utero may be associated with an increased risk of spontaneous abortion in adulthood. However, this may be a chance finding due to multiple comparisons. Similar associations should be explored in additional studies with more refined estimates of childhood and in utero exposure to tobacco smoke.

Abortion, Spontaneous↗

PubMed2002

Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation.

Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor-alpha production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients.

Adipose Tissue↗

PubMed1999

Neonatal screening for hearing disorders in infants at risk: incidence, risk factors, and follow-up.

OBJECTIVE: To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. SETTINGS: Multicenter prospective trial at five centers in Germany. METHODS: Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, critical hyperbilirubinemia, ototoxic medications, bacterial meningitis, postnatal asphyxia, mechanical ventilation >5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight <10th percentile, persistent pulmonary hypertension, and intracranial hemorrhage more than or equal to grade III or periventricular leukomalacia on infant hearing were evaluated. The screening procedure was performed by automated auditory brainstem response (A-ABR; ALGO 1-plus; Natus Med Inc, San Carlos, CA). STATISTICS: univariate analyses of risk factors versus A-ABR results and a multivariate regression analysis were used; additionally, the total test time was recorded. RESULTS: Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 +/- 4.3 weeks, birth weight 2141 +/- 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. CONCLUSION: Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Analysis of Variance↗

PubMed1994

Treatment of tumour-induced hypercalcaemia with the bisphosphonate pamidronate: dose-response relationship and influence of tumour type.

BACKGROUND: Patients with humoral hypercalcaemia of malignancy appear to respond less well to biphosphonate therapy than hypercalcaemic patients with osteolytic metastases. On the other hand, pamidronate is currently the most potent of the commercially available biphosphonates and it is recommended that its dose be increased as a function of pretreatment calcium levels. PATIENTS AND METHODS: We reviewed our experience with pamidronate in 160 patients with tumour-induced hypercalcemia (TIH) persisting after rehydration, particularly the influence of the dose administered, the tumour type and the presence of bone metastatic involvement on the calcaemic and calciuric response to pamidronate therapy. RESULTS: Serum Ca was normalized in 92% of the cases (87% when Ca was corrected for protein levels). After therapy, 59% of the patients developed asymptomatic hypocalcaemia (30% for Corr. Ca levels). A multiparameter regression analysis revealed that the response to pamidronate was significantly (P < 0.01) influenced by initial Ca levels up to days 5-7 and, thereafter, only by the dose received. To confirm the dose effect, we divided the patients into three groups according to the median dose received, namely 0.5 mg/kg (n = 35), 1.0 mg/kg (n = 52), and 1.5 mg/kg (n = 73). The differences among the three groups became significant (P < 0.05) from days 5-7 until the end of the evaluation (days 22-26). Similarly, the success rate, considering Corr. Ca levels, was 80% for the 0.5 and 1.0 mg/kg groups combined, compared to 94% for the 1.5 mg/kg group (P < 0.05). The duration of normocalcaemia was similarly more prolonged in the high-dose group. There was a dose-response relationship only in patients with Ca levels above 3.0 mmol/L and in patients with an elevated index of tubular calcium reabsorption. By contrast, the decrease in Ca levels and in fasting urinary calcium excretion, a sensitive index of bone resorption, were not significantly influenced by the primary tumour site or by the presence of bone metastatic involvement. CONCLUSIONS: Our data demonstrate a dose-response relationship for pamidronate in TIH over an efficient hypocalcaemic dose range, at least in patients with an elevated tubular calcium reabsorption, which helps to resolve conflicting data in the literature. We suggest that a dose of around 1.5 mg of pamidronate/kg is optimal for the treatment of TIH, except in patients with mild hypercalcaemia, for whom a dose of 1 mg/kg appears to be sufficient. At these dose levels, the efficacy of pamidronate is not significantly influenced by the tumour type or the degree of metastatic bone involvement.

Adult↗

PubMed2006

Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163.

OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.

Adult↗