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Early detection and screening for ovarian cancer: does physician specialty matter?

OBJECTIVE: To examine physician factors associated with ovarian cancer screening. METHODS: Postal questionnaires to Maryland primary care physicians. Bivariate tests for statistical significance used X-Square and Student's t tests. Multivariate analysis and logistic regression were used to analyze responses based on specialty type, gender, and work experience. RESULTS: Fifty-six percent of the 375 were male, 44%, females; 33%, OB/GYN; and 67%, family/internal medicine (FM/IM). The mean age was 47 and the mean number of years in practice was 16. OB/GYNs provided more ovarian cancer counseling, OR 2.64 (CI 1.55, 4.48) and were more likely to respond correctly to knowledge questions--i.e., reduction of ovarian cancer risk with oral contraceptive (OCP) use than IM/FM, OR 8.57 (CI 3.54, 20.8). Overall, there were few gender differences in approach to evaluation, but male physicians were less likely to be aware of the relationship of OCP use to ovarian cancer risk than females, OR 0.48 (CI 0.25, 0.91). IF/FM physicians were less likely to order CA-125 for patients (of any age) based upon symptoms of bloating or physical examination alone. OB/GYN physicians, OR 4.77 (2.73, 8.34) and physicians with > 15 years in practice, OR 2.79 (1.46, 5.35) attended more meetings on ovarian cancer than non OB/GYNs or those with less experience. Although 74% indicated access to the Internet, just 16% to 26% used the Internet for cancer information; OB/GYNs used the Internet less frequently than FM/IMs, OR 0.53 (0.28, 0.97). CONCLUSIONS: Specialty was more predictive of knowledge, approach to evaluation, and counseling than gender or experience.

Clinical Competence↗

Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee.

40 Hemophilia Centers from the USA, Canada, Europe and Japan referred to the International Registry 204 patients with haemophilia A, treated by Immune Tolerance (IT) Protocols over the past two decades because of the presence of an inhibitor to FVIII. 82% of the patients were high responders, while IT was started with low levels of inhibitor (< 10 BU) in most (57.3%) of the cases. 69 patients (33.8%) were given the highest FVIII dosage (> or = 200 IU/kg/day), 71 (34.8%) intermediate dosages (50- < 200) and 64 (31.4%) the lowest dosages (< 50). Of 158 patients persevering with treatment long enough to judge the outcome thereof, 107 (67.7%) achieved tolerance, 12 (7.6%) had a partial response, while 39 (24.7%) did not respond. Multivariate logistic regression analysis showed that two variables were independently associated with the highest probability of success: the use of high dose protocols (> or = 100 IU/kg/day) (p < .0001) and the presence of low levels of inhibitor (< 10 BU) at enrollment (p = .004). The Kaplan-Meier inhibitor-free survival curve showed that tolerance is longlasting: only 1 out of 107 patients relapsed and the longest documented tolerant patient has been inhibitor-free for 16 years. 129 hemophiliacs were HIV Ab-negative at enrollment; of the 118 HIV-screened after the treatment, 18 (13.9%) were found to be HIV Ab-positive. IT can indeed modify the natural history of inhibitors to FVIII in hemophilia.

Adolescent↗

Prediction of conductive hearing loss based on acoustic ear-canal response using a multivariate clinical decision theory.

This study evaluated the accuracy of acoustic response tests in predicting conductive hearing loss in 161 ears of subjects from the age of 2 to 10 yr, using as a "gold standard" the air-bone gap to classify ears as normal or impaired. The acoustic tests included tympanometric peak-compensated static admittance magnitude (SA) and tympanometric gradient at 226 Hz, and admittance-reflectance (YR) measurements from 0.5 to 8 kHz. The performance of individual, frequency-specific, YR test variables as predictors was assessed. By applying logistic regression (LR) and discriminant analysis (DA) techniques to the multivariate YR response, two univariate functions were calculated as the linear combinations of YR variables across frequency that best separated normal and impaired ears. The tympanometric and YR tests were also combined in a multivariate manner to test whether predictive efficacy improved when 226-Hz tympanometry was added to the predictor set. Conductive hearing loss was predicted based on air-bone gap thresholds at 0.5 and 2 kHz, and on a maximum air-bone gap at any octave frequency from 0.5 to 4 kHz. Each air-bone gap threshold ranged from 5 to 30 dB in 5-dB steps. Areas under the relative operating characteristic curve for DA and LR were larger than for reflectance at 2 kHz, SA and Gr. For constant hit rates of 80% and 90%, both DA and LR scores had lower false-alarm rates than tympanometric tests-LR achieved a false-alarm rate of 6% for a sensitivity of 90%. In general, LR outperformed DA as the multivariate technique of choice. In predicting an impairment at 0.5 kHz, the reflectance scores at 0.5 kHz were less accurate predictors than reflectance at 2 and 4 kHz. This supports the hypothesis that the 2-4-kHz range is a particularly sensitive indicator of middle-ear status, in agreement with the spectral composition of the output predictor from the multivariate analyses. When tympanometric and YR tests were combined, the resulting predictor performed slightly better or the same as the predictor calculated from the use of the YR test alone. The main conclusion is that these multivariate acoustic tests of the middle ear, which are analyzed using a clinical decision theory, are effective predictors of conductive hearing loss.

Acoustic Impedance Tests↗

Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer.

BACKGROUND: Urokinase-type plasminogen activator (uPA) is a proteolytic enzyme thought to be involved in processes leading to tumor cell invasion of surrounding tissues. Its activity during metastasis may be regulated by an inhibitor, PAI-1. Previous work has shown that high levels of uPA and PAI-1 are associated with poor prognosis in primary breast cancers. PURPOSE: In this pilot study, we explored possible associations between the expression levels of uPA or PAI-1 and the efficacy of tamoxifen treatment in breast cancer patients with relapsed disease. METHODS: Levels of uPA, PAI-1, estrogen receptor (ER), and progesterone receptor (PgR) were assayed in cytosolic extracts derived from the primary breast tumors of 235 tamoxifennaive patients who had recurrent disease. The extracts were classified as positive or negative for each assayed factor. In some analyses, ER and PgR levels were evaluated together. In these analyses, three ER/PgR subsets were defined: low, intermediate, and high. All patients in the study received tamoxifen therapy upon relapse (median follow-up, 57 months). Association of the tested factors with the response to tamoxifen treatment was studied by logistic regression analysis. Association of the factors with progression-free and overall survival was further evaluated by Cox univariate and multivariate regression analyses. RESULTS: Patients with uPA-negative tumors exhibited a better response (tumor regression or stable disease, maintained for more than 6 months) to tamoxifen treatment than those with uPA-positive tumors (51% versus 26% response; odds ratio [OR] = 0.34; 95% confidence interval [CI] = 0.18-0.65). The response rate was also better for patients with PAI-1-negative tumors than for those with PAI-1-positive tumors (49% versus 35% response; OR = 0.57; 95% CI = 0.32-1.01). In addition, patients with uPA-positive or PAI-1-positive tumors showed shorter progression-free survival (P = .001 and P < .05, respectively) and total survival after relapse (P = .005 and P < .005, respectively). When patients were stratified by ER/PgR status, the only statistically significant association between uPA levels and reduced tamoxifen response was seen in the subset whose tumors possessed intermediate levels of ER/PgR (16% response in uPA-positive versus 60% response in uPA-negative tumors; OR = 0.13; 95% CI = 0.04-0.41). Overall, uPA status appeared independent of association with ER/PgR status in its ability to predict response to tamoxifen treatment. The association of PAI-1 expression and the response to tamoxifen was less pronounced when patients were stratified by ER/PgR status. CONCLUSION: Measurement of primary breast tumor uPA levels may be useful in predicting the overall response of metastatic disease to tamoxifen therapy.

Adult↗

Age and radiation response in glioblastoma multiforme.

OBJECTIVE: Advanced age is a strong predictor of shorter survival in patients with glioblastoma multiforme (GM), especially for those who receive multimodality treatment. Radiographically assessed tumor response to external beam radiation therapy is an important prognostic factor in GM. We hypothesized that older GM patients might have more radioresistant tumors. METHODS: We studied radiographically assessed response to external beam radiation treatment (five-level scale) in relation to age and other prognostic factors in a cohort of 301 GM patients treated on two prospective clinical protocols. A total of 223 patients (74%) were assessable for radiographically assessed radiation response. A proportional odds ordinal regression model was used for univariate and multivariate analysis. RESULTS: Younger age (P = 0.006), higher Karnofsky Performance Scale score before radiotherapy (P = 0.027), and more extensive surgical resection (P = 0.028) predicted better radiation response in univariate analyses. Results were similar when clinical criteria were used to classify an additional 61 patients without radiographically assessed radiation response (stable versus progressive disease). In multivariate analyses, age and extent of resection were significant independent predictors of radiation response (P < 0.05); Karnofsky Performance Scale score was of borderline significance (P = 0.07). CONCLUSION: Older GM patients are less likely to have good responses to postoperative external beam radiation therapy. Karnofsky Performance Scale score before radiation treatment and extent of surgical resection are additional predictors of radiographically assessed radiation response in GM.

Brain Neoplasms↗

Adolescent HMO enrollees' utilization of out-of-plan services.

PURPOSE: To examine use of reproductive health services, correlates of out-of-plan care, and reasons for seeking out-of-plan care among adolescent health maintenance organization (HMO) enrollees. METHODS: We mailed a self-administered questionnaire to a population-based random sample of 18-year-old members of Group Health Cooperative of Puget Sound (GHC) who had been enrolled for at least 12 months. The sample was selected from GHC's computerized enrollment database. Questionnaire topics included reproductive history, sexual behavior, and use of health services. Analysis included Chi-square tests to examine differences by gender and out-of-plan status and multivariate analysis using logistic regression. RESULTS: About one-half of the 997 respondents (69% response rate) reported using out-of-plan care. In multivariate analysis, the strongest correlate of out-of-plan care was having had sexual intercourse [odds ratio (OR) = 1.84; 95% confidence interval (CI) = 1.35-2.52]. Other correlates were using alcohol (OR = 1.79; 95% CI = 1.29-2.48), living with parents (OR = 0.65; 95% CI =.46-.92), and being female (OR = 1.60; 95% CI = 1.21-2.11). During the prior year, over 80% of sexually active respondents had obtained contraceptives out-of-plan and 45% of those tested for sexually transmitted diseases (STDs) reported out-of-plan testing. The primary reasons reported for using any out-of-plan care were lack of convenience (28%), being out of town (26%), and confidentiality (23%; only reported by sexually active respondents). CONCLUSIONS: A substantial proportion of GHC-enrolled adolescents used out-of-plan care. Those who did were more likely to have had STDs and other health problems than those who used only in-plan services. Without continuity of care, these at-risk adolescents may not be receiving optimal services.

Adolescent↗

Potential risk factors for infection with Candida spp. in critically ill patients.

The incidence, risk factors and prognostic factors for candidal infection were determined in a prospective study of 280 infected patients. Thirty-one (11%) patients were infected with Candida spp., sub-divided into 18 (58%) with C. albicans, and 13 (42%) with non-albicans spp. (six C. glabrata, three C. parapsilosis, and one each of C. krusei, C. tropicalis, C. guilliermondii and C. lusitaniae). Infection with Candida spp. was always associated with concurrent bacterial infection. By univariate logistic regression analysis, the degree of morbidity and the duration of mechanical ventilation were independent predictive factors for death, but infection with Candida spp., was not. Factors associated with Candida spp. infection were the degree of morbidity, intensive care unit length of stay, alterations of immune response, and the number of medical devices involved. By multivariate logistic regression analysis, the only independent risk factor for candidal infection was intensive care unit length of stay.

Adult↗

Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSIDA study.

OBJECTIVES: To investigate the ability of several HIV-1 drug-resistance interpretation systems, as well as the number of pre-specified combinations of abacavir-related mutations, to predict virological response to abacavir-containing regimens in antiretroviral therapy-experienced, abacavir-naive patients starting an abacavir-containing regimen in the EuroSIDA cohort. PATIENTS AND METHODS: A total of 100 HIV-infected patients with viral load (VL) >500 copies/ml who had a plasma sample available at the time of starting abacavir (baseline) were included. Resistance to abacavir was interpreted by using eight different commonly used systems that consisted of rules-based algorithms or tables of mutations. Correlation between baseline abacavir-resistance mutations and month 6 virological response was performed on this population using a multivariable linear regression model accounting for censored data. RESULTS: The baseline VL was 4.36 log10 RNA copies/ml [interquartile range (IQR): 3.65-4.99 log10 RNA copies/ml] and the median CD4 cell count was 210 cells/microl (IQR: 67-305 cells/microl). Our patients were pre-exposed to a median of seven antiretrovirals (2-12) before starting abacavir therapy. The median (range) number of abacavir mutations (according to the International AIDS Society-USA) detected at baseline was 3.5 (0-8). Overall, the Kaplan-Meier estimate of the median month 6 VL decline was 0.86 log10 RNA copies/ml [95% confidence intervals (95% CI): 0.45-1.24]. The VL in those patients (n=31) who intensified treatment by adding only abacavir decreased by a median 0.20 log10 RNA copies/ml (95% CI: -0.18; +0.94). The proportion of patients who harboured viruses fully resistant to abacavir among the eight genotypic resistance interpretation algorithms ranged from 12% [Agence Nationale de Recherches sur le SIDA (ANRS)] to 79% [Stanford HIV RT and PR Sequence Database (HIVdb)]. Some interpretation systems showed statistically significant associations between the predicted resistance status and the virological response while others showed no consistent association. The number of active drugs in the regimen was associated with greater virological suppression (additional month 6 VL reduction per additional sensitive drug=0.51, 95% CI: 0.15-0.88, P=0.006); baseline VL was also weakly associated (additional month 6 VL reduction per log10 higher=0.30, 95% CI: -0.02; +0.62, P=0.06). In contrast, the number of drugs previously received was associated with diminished viral reduction (additional month 6 VL reduction per additional drug=-0.14, 95% CI: -0.28; 0.00, P=0.05). CONCLUSIONS: Our results revealed a high degree of variability among several genotypic resistance interpretation algorithms currently in use for abacavir. Therefore, the interpretation of genotypic resistance for predicting response to regimens containing abacavir remains a major challenge.

Adult↗

Are there patients with acute ischemic stroke and atrial fibrillation that benefit from low molecular weight heparin?

BACKGROUND AND PURPOSE: Treatment doses of heparins are not recommended for acute ischemic stroke. Despite this, their use in this setting is widespread. We investigated whether subgroups of patients with acute ischemic stroke and atrial fibrillation, identified by clinical, hemostatic (d-dimer, prothombin fragments(1+2) [F(1+2)], soluble fibrin monomer), or inflammatory (C-reactive protein [CRP]) variables might have a differential response to low molecular weight heparin (LMWH) over aspirin. In addition, we sought to identify factors associated with a poor clinical outcome at 3 months. METHODS: We conducted a post hoc subgroup analysis of a randomized, placebo-controlled, double-blind trial (Heparin in Acute Embolic Stroke Trial) designed to test the hypothesis that treatment doses of LMWH (dalteparin; 100 IU/kg BID) would be superior to aspirin (160 mg per day) in patients with acute ischemic stroke and atrial fibrillation. For the current analysis, 431 participants were included. The primary outcome measure was a poor outcome at 3 months, defined as death or dependency in activities of daily living. Using regression analysis, we determined whether any of the chosen variables were associated with a differential response to dalteparin (treatment interaction) or with poor outcome. RESULTS: In the multivariable logistic regression model, none of the clinical, hemostatic, or inflammatory variables were associated with a significant treatment interaction. Stroke severity (odds ratio [OR], 1.09 [95% CI, 1.07 to 1.12]), increasing age (OR, 1.09 [CI, 1.05 to 1.14]), CRP level (OR, 1.32 [CI, 1.04 to 1.66]), and F(1+2) level (OR, 1.77 [CI, 1.07 to 2.91]) were independently associated with a poor outcome at 3 months. CONCLUSIONS: Our study does not support the use of treatment doses of LMWH in any of the studied subgroups of patients with acute ischemic stroke and atrial fibrillation. Age, stroke severity, CRP, and F(1+2) were predictive of poor outcome at 3 months.

Adult↗

Understanding community structure: a data-driven multivariate approach.

Habitat is known to influence community structure yet, because these effects are complex, elucidating these relationships has proven difficult. Multiple aspects of vegetation architecture or plant species composition, for example, may simultaneously affect animal communities and their constituent species. Many traditional statistical approaches (e.g., regression) have difficulty in handling large numbers of collinear variables. On the other hand, multivariate methods, such as ordination, are well suited to handle these large datasets, but they have primarily been used in ecology as descriptive techniques, and less frequently as a data reduction tool for predictor variables in regression. Here, I employ a multivariate approach for variable reduction of both the predictor and response variables to investigate the influences of vegetation architecture and plant species on community composition in spiders using multiple regression. This allows retention of the information in the original dataset while producing statistically tractable variables for use in further analyses. I used nonmetric multidimensional scaling to reduce the number of variables for predictor (habitat architecture and plant species) and response (spider species) data matrices, and used these new variables in multiple regression analyses. These axes can be interpreted based on their correlations with the original variables, allowing for recovery of biologically meaningful information from regressions. Consequently, the important variables are determined by the data themselves, rather than by a priori assumptions of the researcher. Contrary to expectations based on previous work in spiders and other animals, plant species composition explained more variation in spider communities than did habitat architecture, and was also a stronger predictor of other community structure variables (overall abundance, species richness, and species diversity). I discuss possible ecological explanations for these results, and the advantages of the proposed method.

Animals↗

Urine Proteomics as a Source of Biological Information and Outcome Predictor in Living Kidney Transplantation.

Kidney transplantation (KTx) is the preferred treatment for kidney failure. However, post-transplant management is challenging due to the limited lifespan of transplanted organs. Current methods for monitoring post-transplant complications are invasive and have limitations. Therefore, there is an urgent need for novel non-invasive biomarkers. This study investigates the proteomic composition of urine to understand renal biology during the process of transplantation and to identify potential markers for outcome prediction. Urine samples were collected from donors before transplantation and from recipients 4 weeks and 1 year after transplantation. Proteomic analysis was performed using mass spectrometry and label-free quantification. Statistical analyses included principal component analysis (PCA) and enrichment analysis. The resulting key findings were confirmed in an independent validation cohort. In addition, correlative regression models to evaluate the relationship between protein abundance and clinical outcomes in the further course after transplantation were performed. 106 urine samples in the setting of 70 kidney transplantations were analyzed. PCA revealed distinct clustering of donor and recipient samples, indicating significant proteomic changes after transplantation. Hierarchical clustering and gene ontology analysis identified molecular changes as a response to transplantation and showed an over-representation of relevant pathways related to inflammation, cell immune response and coagulation in both the original and validation cohorts. Multivariate regression analysis, including linear and logistic regression, identified 11 potential protein biomarkers, including ORM2, IL1RAP, APP, and FABP4 as predictors of eGFR 12 months after transplantation and 1 HP as a predictor of infections within the first year after transplantation, respectively. This study underscores the potential of non-invasive urine proteomics for identifying biological processes involved in kidney transplantation and for enhancing post-transplant monitoring and outcome prediction. We identified 12 potential biomarkers with added value to standard clinical parameters linked to transplant outcomes, which will be promising candidates for future outcome monitoring after KTx.

Humans↗

Quantitative analysis of p53 protein in non-small cell lung cancer and its prognostic value.

Accumulation of mutant p53 protein occurs frequently in human malignancies, including 40-60% of non-small cell lung carcinomas. The implications of such p53 over-expression, usually assessed by immunohistochemical techniques, for the prognosis of lung cancer patients remain undetermined. In this study, we used a time-resolved immunofluorometric assay to measure p53 protein concentrations in extracts prepared from 86 primary non-small cell lung tumours and examined the associations between p53 protein levels (corrected for total protein) and other clinico-pathologic variables, including post-surgical disease-free and overall survival. Contingency tables analysed by chi2 tests revealed no significant relationships between p53 status, defined by a median cut-off point, and patient gender, age, disease stage, histologic grade and type, lymph node extension, smoking history and administration of adjuvant chemotherapy or radiation. However, multivariate Cox proportional hazard regression analysis demonstrated a dose-response relationship between p53 concentration, expressed as a 4-level, quartile-divided variable, and increased risk of relapse (p = 0.010) and death (p = 0.016). Patients whose tumours contained p53 concentrations exceeding the median value had over 3-fold higher risk of relapse (p = 0.002) and death (p = 0.007) than those whose tumours had lower p53 concentrations. We also provide evidence suggesting that the impact of p53 on survival is greater in patients with squamous cell carcinoma than in those with adenocarcinoma. Although the latter finding needs confirmation, our results suggest that application of an immunoassay of p53 protein on non-small cell lung tumour extracts may identify patients at increased risk of unfavourable outcome.

Adenocarcinoma↗

Prognostic value of histopathologic parameters in squamous cell carcinoma of the oropharynx.

Seventy-seven patients with squamous cell carcinoma of the oropharynx were treated by preoperative radiation therapy (4000-5000 rad) followed by surgical resection. The original biopsy specimens were evaluated for degree of keratinization, nuclear pleomorphism, frequency of mitoses, inflammatory response, vascular invasion, and pattern of invasion. Multivariant analysis (Cox regression model) and life table survival function were used to determine the relative contributions of the clinical and histologic parameters to patient outcome. The results were as follows: (1) large tumor size, nodal metastases, and male sex were found to be predictive of a poorer survival (P = 0.004, 0.0167, and 0.0237, respectively); and (2) an analysis of a combination of clinical and histologic parameters demonstrated that the pattern of invasion was the only histologic factor that was predictive of survival (P = 0.0436). Neoplasms invading as large cohesive aggregates indicated a better prognosis than neoplasms invading as thin, irregular cords or individual cells. Restricting the statistical evaluation to only histologic factors (excluding clinical factors) demonstrated that increased frequency of mitoses also correlated with poor survival (P = 0.0218). Further restriction of the analysis to T2 and T3 neoplasms that have similar survival times indicated that both frequency of mitoses and pattern of invasion were of prognostic value in predicting survival (P = 0.0127 and 0.0168, respectively).

Carcinoma, Squamous Cell↗

Risk Factors for Breakthrough Acute SARS-CoV-2 Infections in Fully Vaccinated Individuals: A Case-Control Study Nested in a Prospective Cohort in Medelln, Colombia.

To effectively curb coronavirus disease 2019 (COVID-19), it is essential to understand the risk factors for breakthrough acute infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) despite vaccination. We conducted a case-control study to assess risk factors for acute SARS-CoV-2 infections requiring hospitalization in vaccinated individuals. The study included 50 vaccinated patients who experienced breakthrough infections requiring hospitalization (inpatient cohort) and 250 control participants from the outpatient cohort of the "Genomic Surveillance and Immune Response Monitoring for COVID-19 in the Metropolitan Area of the Aburr&#xe1; Valley, Medell&#xed;n-Colombia". Demographic characteristics, vaccination status, and immune responses were compared between cases and controls using multivariate logistic regression. Advanced age (&#x2265;&#x2009;65 years), male sex, high-risk comorbidities, and immunosuppression were associated with an increased risk of breakthrough SARS-CoV-2 infections despite prior vaccination. In contrast, receipt of a booster dose and the presence of neutralizing antibodies were linked to a reduced risk of such infections. This study identifies key risk and protective factors associated with breakthrough SARS-CoV-2 infections. Derived from a high-middle-income setting, these real-world findings provide valuable insights to guide targeted vaccination strategies for vulnerable populations.

Humans↗

[Sex-specific utilization of medical aid. Results of the Munich Blood Pressure Study].

Sex differences in the frequency of physician visits, participation in cancer screening tests, number of drugs consumed, intake of antihypertensive drugs, and participation in hypertension screening have been investigated with data from the Munich Blood Pressure Study I and II (MBS 1981 and 1982). The study population was a random sample of the adult population of Munich (30-69 yrs.). 2216 men and women participated in MBS I (response 69.3%). The results from descriptive analyses and multivariate logistic regression showed significant relationships between sex and the various types of medical care utilization described above, with the exception of participation in hypertension screening, that is participation in the Munich Blood Pressure Study. Also, after controlling for age, marital status, education, occupational position, subjective physical well-being, number of chronic diseases, women went more often to the doctors and consumed more drugs than men. The sex differences were the largest in the participation of cancer screening tests (odds ratio 7.7), and the smallest in the frequency of physician visits (odds ratio 1.8) and participation in hypertension screening (not significant). Additionally, the sex differences in medical care utilization decreased with age.

Adult↗

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort.

AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

Aged↗

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.

Adult↗

The reliability and validity of a new and simple method to measure sedation levels in intensive care patients: a pilot study.

BACKGROUND: Since more sophisticated ventilation techniques have enabled patients to comply with the ventilator with little or no sedation, deep sedation levels can easily be avoided. However, successful ventilation techniques also expanded the treatment possibilities for more severely ill patients who require deeper sedation levels. We developed a new sedation score to improve the prevention of oversedation and to simplify scoring practice in the intensive care unit (ICU). OBJECTIVE: The study's objective was to establish the validity and reliability of a new sedation score (Sedic score) for critically ill, sedated adult patients. METHODS: We prospectively evaluated the reliability and validity of the Sedic score. The study took place in a 30-bed ICU in a university teaching hospital. Forty-six consecutive mechanically ventilated and sedated ICU patients were included. The constructed scale consists of five levels of stimuli and five levels of responses. Sedation levels are defined by the sum of stimulus and response. The reliability of the Sedic score was assessed by simultaneous measurement by the research nurse and attending nurse (n=70). VALIDITY was expressed as (1) the hierarchic relation between stimulus and response (n=443), (2) the prediction of wake-up time by the Sedic score (n=46), and (3) the association between the Sedic score and the Ramsay scale (n=88). RESULTS: The method showed excellent reliability. VALIDITY: Weighted kappa between stimulus and response was .82. Multivariate analysis: (recovery time as independent variable) regression line (Y=-2.53+ 2.16 * beta; P<.001) (r2=42%). Correlation between the Sedic scores and the Ramsay scores was r(s) .74 (P=.01). Sixty-seven percent of the patients with a maximum Ramsay score of 6 had scores ranging between 6 and 10 on the Sedic scale, indicating that the Ramsay scale has a serious ceiling effect. CONCLUSION: The Sedic score demonstrates sufficient reliability and validity, and correlates well with wake-up time. It allows for frequent use by nurses to avoid oversedation in patients.

Adult↗