Number and sequence of preceding miscarriages and maternal age for the prediction of antiphospholipid syndrome in women with recurrent miscarriage.

OBJECTIVE: To investigate the relationship between the number and sequence of preceding miscarriages and antiphospholipid syndrome (APS). DESIGN: Retrospective cohort study. SETTING: Recurrent miscarriage (RM) clinic. PATIENT(S): Women who attended the RM clinic from 1988 to 2006. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number, type, and sequence of previous pregnancies were compared between women with APS and women with unexplained RM. RESULT(S): A total of 1,719 patients were included; 312 (18%) had APS, and 1,407 (82%) had unexplained RM. The mean maternal age (32.6 years) did not differ between women with and without APS. The median number of miscarriages was three in both groups. A total of 865 women (50%) had a history of at least one live birth, with no difference between the two groups. In both groups, 97% of the women had a history of consecutive miscarriages. CONCLUSION(S): The number of preceding miscarriage, type and sequence of previous pregnancies, and maternal age were not associated with APS in women with RM. There is no increased diagnostic yield for APS after three miscarriages rather than after two miscarriages and no increased diagnostic yield for APS after consecutive miscarriages rather than after nonconsecutive miscarriages. Therefore, APS testing should be considered for all women with two or more miscarriages.

The prediction of functional decline in older hospitalised patients.

BACKGROUND: thirty to sixty per cent of older patients experience functional decline after hospitalisation, associated with an increase in dependence, readmission, nursing home placement and mortality. First step in prevention is the identification of patients at risk. OBJECTIVE: to develop and validate a prediction model to assess the risk of functional decline in older hospitalised patients. DESIGN: development study: cohort study (n = 492). Validation study: secondary data analysis of a cohort study (n = 484) in an independent population. Both with follow-up after 3 months. Functional decline was defined as a decline of at least one point on the Katz ADL index at follow-up compared with pre-admission status. SETTING: development study: general internal medicine wards of two university hospitals and one regional hospital. Validation study: general internal wards of an university hospital. SUBJECTS: patients ≥65 years acutely admitted and hospitalised for at least 48 h. RESULTS: thirty-five per cent of all patients in the development cohort and 32% in the validation cohort developed functional decline. A four-item model could accurately predict functional decline with an AUC of 0.71. At threshold 2 sensitivity, specificity, positive and negative predictive values were 87, 39, 43 and 85%, respectively. In the validation study, this was, respectively, 0.68, 89, 41, 41 and 89%. CONCLUSION: pre-admission need for assistance in instrumental activities of daily living, use of a walking device, need for assistance in travelling and no education after age 14, are the items of a prediction model to identify older patients at risk for functional decline following hospital admission. The strength of the model is that it relies on four simple questions and this makes it easy to use in clinical practice and easy to administer.

Chromosomal mosaicism in human preimplantation embryos: a systematic review.

BACKGROUND: Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is determined by the analysis of a single cell from that embryo. METHODS: Here we report a systematic review and meta-analysis of studies on the chromosomal constitution of human preimplantation embryos. In 36 studies, out of 2117 citations that met our search criteria, data were provided extensively enough to allow classification of each analysed embryo with prespecified criteria for its chromosomal makeup. The main outcome of this classification was the prevalence of chromosomal mosaicism in human preimplantation embryos. RESULTS: A total of 815 embryos could be classified. Of these, 177 (22%) were diploid, 599 (73%) were mosaic, of which 480 (59% of the total number of embryos) were diploid-aneuploid mosaic and 119 (14% of the total number of embryos) were aneuploid mosaic, and 39 (5%) contained other numerical chromosomal abnormalities. The distribution of the embryos over these categories was associated with the developmental stage of the embryos, the method used for analysis and the number of chromosomes analysed. CONCLUSIONS: Diploid-aneuploid mosaicism is by far the most common chromosomal constitution in spare human preimplantation embryos after IVF. This undermines the reliable determination of the ploidy status of a cleavage-stage embryo based on the analysis of a single cell. Future research should determine the origin and developmental potential of mosaic embryos.

Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model.

BACKGROUND: Declining residual renal function, as indicated by the glomerular filtration rate (GFR), is associated with an increased mortality risk in patients with end-stage renal disease (ESRD) on dialysis. METHODS: We monitored GFR and mortality in 1800 haemodialysis (HD) and peritoneal dialysis (PD) patients in 1996-2006. We used a marginal structural model to estimate the causal effects both of GFR when it was not completely lost and of the subsequent full loss of GFR on mortality, avoiding the drawbacks of standard regression models that include covariates to adjust for confounding. Instead, effect estimates were adjusted for possible baseline and time-varying confounders using inverse probability weighting. RESULTS: We estimated a hazard ratio (HR) corresponding to the effect of the full loss of GFR on mortality, as compared to not having fully lost GFR, of 1.50 [95% confidence interval (CI) 1.09-2.07]. The HR corresponding to the effect of GFR when GFR is not (yet) fully lost on mortality was 0.97 (95% CI 0.92-1.02) (per mL/min/1.73 m(2)). We found no significant difference in the effect of GFR on mortality between patients starting on PD and HD. CONCLUSIONS: Preventing or delaying the full loss of GFR can improve survival in dialysis patients. This supports the importance that is given to the effect of treatment options for patients with ESRD on the rate of decline of the residual renal function.

Risk for poor outcomes in older patients discharged from an emergency department: feasibility of four screening instruments.

OBJECTIVES: To compare the prognostic value of four screening instruments used to detect the risk for poor outcomes [in terms of likelihood of recurrent emergency department (ED) visits, hospitalizations, or mortality] for older patients discharged home from an ED in the Netherlands. METHODS: This is a prospective cohort study, which included all consecutive patients of at least 65 years discharged from the ED of a university teaching hospital in the Netherlands, between 1 December 2005, and 1 November 2006. Four screening instruments were tested: the identification of seniors at risk, the triage risk screening tool, and the Runciman and Rowland questionnaires. The cutoff of the Runciman questionnaire was adapted and the age cutoff was adapted for the other instruments. Recurrent ED visits, subsequent hospitalization, and mortality within 30 and 120 days after the index visit were collected from administrative data. RESULTS: In total, 381 patients were included, with a mean age of 79.1 years. Within 120 days, 14.7% of the patients returned to ED, 17.2% were hospitalized, and 2.9% died. The area under the curve was low for all instruments (between 0.43 and 0.60), indicating poor discriminatory power. CONCLUSION: Older ED patients discharged home are at higher risk of poor outcomes. None of the instruments were able to clearly discriminate between patients with and without poor outcomes. Differences in organization of the health care systems might influence the prognostic abilities of screening instruments.

Pregnancy outcome after preimplantation genetic screening or natural conception in couples with unexplained recurrent miscarriage: a systematic review of the best available evidence.

The objective of this systematic review was to assess live birth rates and miscarriage rates after preimplantation genetic screening or natural conception for unexplained recurrent miscarriage. There were no randomized controlled trials or comparative studies found on this topic. Until data from randomized controlled trials become available, this review summarizes the best available evidence of the efficacy of preimplantation genetic screening vs. natural conception.

Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

PURPOSE: To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). METHODS: Multicenter prospective observational cohort study in patients ≥18 years old and with expected ICU stay ≥72 h. The RIFLE class for AKI was calculated daily, while sCyC and uCyC were determined on days 0, 1, and alternate days until ICU discharge. Test characteristics were calculated to assess the diagnostic performance of CyC. RESULTS: One hundred fifty-one patients were studied, and three groups were defined: group 0 (N = 60), non-AKI; group 1 (N = 35), AKI after admission; and group 2 (N = 56), AKI at admission. We compared the two days prior to developing AKI from group 1 with the first two study days from group 0. On Day -2, median sCyC was significantly higher (0.93 versus 0.80 mg/L, P = 0.01), but not on Day -1 (0.98 versus 0.86 mg/L, P = 0.08). The diagnostic performance for sCyC was fair on Day -2 [area under the curve (AUC) 0.72] and poor on Day -1 (AUC 0.62). Urinary CyC had no diagnostic value on either of the two days prior to AKI (AUC <0.50). RRT was started in 14 patients with AKI; sCyC and uCyC determined on Day 0 were poor predictors for the need for RRT (AUC ≤0.66). CONCLUSIONS: In this study, sCyC and uCyC were poor biomarkers for prediction of AKI and the need for RRT.

Variability in measuring (instrumental) activities of daily living functioning and functional decline in hospitalized older medical patients: a systematic review.

OBJECTIVE: To study instruments used and definitions applied in order to measure (instrumental) activities of daily living (I [ADL]) functioning and functional decline in hospitalized older medical patients. STUDY DESIGN: We systematically searched Medline, Embase, and the Cochrane Database of Systematic Reviews from 1990 to January 2010. Articles were included if they (1) focused on acute hospitalization for medical illness in older patients; (2) described the instrument used to measure functioning; and (3) outlined the clinical definition of functional decline. Two reviewers independently extracted data. RESULTS: In total, 28 studies were included in this review. Five different instruments were used to measure functioning: the Katz ADL index, the IADL scale of Lawton and Brody, the Barthel index, Functional Independence Measure, and Care Needs Assessment. Item content and scoring between and within the instruments varied widely. The minimal amount for decline, as defined by the authors, referred to a decrease in functioning between 2.4% and 20.0%. CONCLUSION: This review shows there is a large variability in measuring (I)ADL functioning of older hospitalized patients and a large range of clinical definitions of functional decline. These conceptual and clinimetric barriers hamper the interpretation and comparison of functional outcome data of epidemiological and clinical studies.

Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients.

BACKGROUND: Previous studies have shown that simple imaging methods may be useful for detection of vascular calcifications in dialysis patients. Based on annual, plain chest X-rays during follow-up on dialysis, we studied the associations of mineral metabolism with the presence and progression of aortic calcification. In addition, we assessed the impact of aortic calcification on mortality. METHODS: Three hundred and eighty-four patients who started haemodialysis or peritoneal dialysis between 1997 and 2007 were included (age 61 ± 15 years, 64% male, 61% haemodialysis). Annual chest X-rays were screened for calcification in the aortic arch, and patients were categorized as having no, moderate or severe calcification. Progression was defined as an increase in calcification category during follow-up on dialysis. RESULTS: At baseline, 96 (25%) patients had severe, 205 (53%) patients had moderate and 83 (22%) patients had no aortic calcification. For 237 of the 288 patients with no or moderate calcifications at baseline, X-rays were available for follow-up. During follow-up (mean 2.3 years), aortic calcification progressed in 71 patients (30%). We found that baseline plasma calcium > 9.5 mg/dL and iPTH > 300 pg/mL were associated with progression [odds ratios of 3.1, 95% confidence interval (1.2-8.2) and 4.4 (1.4-14.1), respectively]. Progression of aortic calcification was significantly associated with increased risk of all-cause mortality (hazard ratio: 1.9; 95% CI: 1.2-3.1) and cardiovascular mortality (hazard ratio: 2.7; 95% CI: 1.3-5.6). CONCLUSIONS: Aortic calcification progressed in almost a third of the patients during dialysis. Hypercalcaemia and hyperparathyroidism were associated with an increased risk of progression. Progression of aortic calcification was significantly related to an increased mortality risk.

Assessing the prevalence of modifiable risk factors in older patients visiting an ED due to a fall using the CAREFALL Triage Instrument.

OBJECTIVE: Falls in older people are a common presenting complaint. Knowledge of modifiable risk factors may lead to a more tailored approach to prevent recurrent falls and/or fractures. We investigated prevalence of 8 modifiable risk factors for recurrent falling and/or a serious consequence of the fall among older patients visiting the emergency department after a fall with the Combined Amsterdam and Rotterdam Evaluation of Falls Triage Instrument (CTI), a self-administrated questionnaire that consists of questions concerning demographics, possible cause(s) of the fall, and questions relating to (modifiable) risk factors for falling. METHODS: After treatment for their injuries, 1077 consecutive patients 65 years or older visiting the accident and emergency department due to a fall were evaluated by the CTI. The following were assessed: impaired vision, mobility disorder, fear of falling, mood disorder, high risk of osteoporosis, orthostatic hypotension, incontinence, and polypharmacy. RESULTS: The percentage of respondents who returned the questionnaire was 59.3%. The mean (SD) age was 78.5 (7.5) years, and 57.8% experienced a fall with serious consequences. There were 60.9% of patients with a recurrent fall versus 51% with a first fall who experienced with a serious consequence (P = .025). Age and risk factors mobility disorder (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3), high risk of osteoporosis (OR, 2.0; 95% CI, 1.2-3.2), incontinence (OR, 1.7; 95% CI, 1.0-2.7), fear of falling (OR, 2.2; 95% CI, 1.3-3.7), and orthostatic hypotension (OR, 2.4; 95% CI, 1.4-4.2) were independently associated with a recurrent fall. Age and high risk of osteoporosis were the only risk factors predicting a serious consequence of a fall (OR, 4.6; 95% CI, 2.9-7.2). CONCLUSIONS: Age and 5 modifiable risk factors assessed with the CTI were independently associated with a recurrent fall. Only high risk of osteoporosis was associated with a serious consequence.

Cortisol, interleukins and S100B in delirium in the elderly.

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1pg/ml) and cortisol (666, 95% CI: 475-859nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microg/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker.

Identification of older hospitalised patients at risk for functional decline, a study to compare the predictive values of three screening instruments.

AIMS AND OBJECTIVES: To establish a screening instrument for identifying older hospitalised patients at risk for functional decline by comparing the predictive values of three screening instruments: identification of seniors at risk, care complexity prediction instrument and hospital admission risk profile. BACKGROUND: After being hospitalised, 30-60% of older patients experience a decline in functioning, resulting in a decreased quality of life and autonomy. DESIGN: A prospective cohort study. METHODS: Included were patients, aged 65 years and older, acutely admitted to a general internal ward of a university teaching hospital. Within 48 hours after hospital admission, baseline data were completed--demographic, cognitive, social and pre-admission functional status and the screening instruments. Three months after discharge, functional status was measured by telephone interview. The Katz index was used to measure functional status (six activities). Functional decline was defined as a decline of at least one point on the Katz index at three months after discharge compared to pre-admission state. RESULTS: Included were 177 patients; mean age was 77.6 years and 51.7 % were male. Functional decline was found in 27.8% of all patients. Sensitivity, specificity and area under receiver operating curve for identification of seniors at risk (ISAR) were 93, 39% and 0.67, respectively. The corresponding results for the care complexity prediction instrument (COMPRI) were 70, 62% and 0.69 and for the hospital admission risk profile (HARP) 21, 89% and 0.56. CONCLUSION: The discriminative values of both identification of seniors at risk and care complexity prediction instrument are fair. Hospital admission risk profile shows the poorest results. Identification of seniors at risk shows the best ability to predict those patients at risk for functional decline and seems to be the easiest instrument in clinical practice. RELEVANCE TO CLINICAL PRACTICE: Identifying patients at risk for functional decline is a first step in prevention, followed by geriatric assessment and targeted interventions. Studying the validity of existing instruments is necessary before implementation in clinical practice.

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial.

INTRODUCTION: Recent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation. METHODS: We performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality. RESULTS: One hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury. CONCLUSIONS: Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation. TRIAL REGISTRATION: ISRCTN82533884.

The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis.

Delirium is the most common neuropsychiatric syndrome in elderly ill patients. Previously, associations between delirium and the dopamine transporter gene (solute carrier family 6, member 3 (SLC6A3)) and dopamine receptor 2 gene (DRD2) were found. The aim of this study was to validate whether markers of the SLC6A3 and DRD2 genes are were associated with delirium in independent populations. Six European populations collected DNA of older delirious patients. Associations were determined per population and results were combined in a meta-analysis. In total 820 medical inpatients, 185 cardiac surgery patients, 134 non-cardiac surgery patients and 502 population-based elderly subjects were included. Mean age was 82 years (SD 7.5 years), 598 (36%) were male, 665 (41%) had pre-existing cognitive impairment, and 558 (34%) experienced delirium. The SLC6A3 rs393795 homozygous AA genotype was more frequent in patients without delirium in all populations. The meta-analysis showed an Odds Ratio (OR) for delirium of 0.4 (95% confidence interval (C.I.) 0.2-0.6, P = 0.0003) for subjects with AA genotype compared to the AG and GG genotypes. SLC6A3 marker rs1042098 showed no association with delirium. In meta-analysis the DRD2 rs6276 homozygous GG genotype showed an OR of 0.8 for delirium (95% C.I. 0.6-1.1, P = 0.24). When subjects were stratified for cognitive status the rs6276 GG genotype showed ORs of 0.6 (95% C.I. 0.4-1.0, P = 0.06) and 0.8 (95% C.I. 0.5-1.5, P = 0.51) for delirium in patients with and without cognitive impairment, respectively. In independent cohorts, a variation in the SLC6A3 gene and possibly the DRD2 gene were found to protect for delirium.

Perspectives of couples with high risk of transmitting genetic disorders.

OBJECTIVE: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios for PGD versus PND, as PGD treatment is regularly accompanied by waiting lists. DESIGN: Questionnaire study. SETTING: Patient organizations representing genetic disorders. PATIENT(S): A total of 210 couples carrying genetic disorders. MAIN OUTCOME MEASURE(S): Preference for PGD or PND and familiarity with PGD in carrier couples. RESULT(S): Fifteen organizations representing 38 genetic disorders agreed to participate. Nine hundred eighty-three couples responded. In total 210 couples were in their reproductive years (women 18-40 years) and had a desire to conceive. Ninety couples (42%) had never heard of PGD. After they were informed, 127 couples (60%) wanted to have diagnostic testing (PND or PGD) performed. Ninety-four (74%) of these couples preferred testing with PGD. When no waiting list was used 102 couples (80%) preferred PGD. With a 2-year waiting list for PGD, 58 couples (46%) would opt for PGD. CONCLUSION(S): Many carrier couples are unaware of the existence of PGD. When informed, most couples prefer PGD more than PND. The preference for PGD decreases with longer waiting lists.

Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium.

Dopamine excess appears to be critical in the final common pathway of delirium. The aim of this study was to investigate whether genetic polymorphisms in three dopamine-related genes (the dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), and the dopamine transporter (SLC6A3) gene) were associated with delirium. Patients aged 65 years and older acutely admitted to the medical department or to the surgical department following hip fracture were included. Delirium was diagnosed by the Confusion Assessment Method. Sixteen single nucleotide polymorphisms (SNPs) and one variable number of tandem repeats in the SLC6A3 gene, nine SNPs in the DRD2 gene, and six SNPs in the DRD3 gene were genotyped. Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older and had more frequently pre-existing functional and cognitive impairment (P < 0.001). After correction for multiple testing, one SNP in the SLC6A3 gene (rs393795) was associated with reduced risk of delirium (P = 0.032). Adjusted for age, cognitive impairment, and functional impairment, three SNPs in the DRD2 gene and seven SNPs in the SLC6A3 gene were associated with delirium; none of these associations was significant after correction for multiple testing. Variations in the SLC6A3 gene and possibly the DRD2 gene were associated with delirium. Although validation of these results is needed our results support a role for the dopamine transporter and dopamine receptor 2 in the pathogenesis of delirium.

Low uptake of prenatal diagnosis after established carrier status of a balanced structural chromosome abnormality in couples with recurrent miscarriage.

OBJECTIVE: To evaluate to what extent couples carrying a balanced structural chromosome abnormality follow up the advice to opt for invasive prenatal diagnosis (PND) in subsequent pregnancies. DESIGN: Index-control study. SETTING: Six centers for Clinical Genetics in The Netherlands. PATIENT(S): Couples referred for chromosome analysis after recurrent miscarriage between 1992 and 2001 and with at least one pregnancy after disclosure; 239 carrier couples and 389 noncarrier couples. INTERVENTION(S): Questionnaire, medical record checking. MAIN OUTCOME MEASURE(S): Uptake of invasive PND. RESULT(S): Only 53 of 239 (22%) carrier couples underwent a PND procedure (CVS or amniocentesis) in all subsequent pregnancies. A relatively high number, 105 (44%) carrier couples, refrained from PND in all subsequent pregnancies. More carrier couples with maternal age >or=36 years (20/33 = 61%) refrained from PND, compared with carrier couples with maternal age <36 years (85/206 = 41%). In women >or=36 years, an equal proportion of carrier and noncarrier couples refrained from PND (61% vs. 54%). CONCLUSION(S): The advice to opt for invasive PND in carrier couples is poorly followed, especially in carrier couples with maternal age >or=36 years. The motivations of carrier couples to opt for or refrain from invasive PND procedures should be the topic for further research to optimize clinical care and informative decision making.

Serum S100B in elderly patients with and without delirium.

OBJECTIVE: Elevation of S100B has been shown after various neurologic diseases with cognitive dysfunction. The aim of this study was to compare the serum level of S100B of patients with and without delirium and investigate the possible associations with different subtypes of delirium. METHODS: Acutely admitted medical patients aged 65 years or more were included from 2005 through 2008. Delirium was diagnosed by Confusion Assessment Method, delirium subtype by Delirium Symptom Interview and preexistent global cognitive function by the 'Informant Questionnaire on Cognitive Decline-short form'. S100B levels were determined in serum by electrochemiluminescence immunoassay. RESULTS: Samples of 412 patients were included, 91 during delirium, 35 after delirium and 286 of patients without delirium. Patients with delirium (31%) were significantly older, 81.5 versus 76.6 years (p < 0.001) and experienced significantly more often preexistent cognitive and functional impairment (p < 0.001). S100B level differed significantly (p = 0.004) between the three groups: median 0.07 microg/L (inter-quartile ranges: 0.05-0.14 microg/L) during delirium, 0.12 microg/L (0.05-0.29 microg/L) after delirium and 0.06 microg/L (0.03-0.10 microg/L) in patients without delirium. Combining the impact of cognitive impairment, infection and age on S100B, highest S100B was observed in the oldest patients after delirium with preexistent cognitive impaired and infection. Delirium subtype and S100B level were not significantly correlated. CONCLUSION: Higher S100B levels were found in patients with delirium than in patients without delirium, with highest levels of S100B in samples taken after delirium. Future studies are needed to elucidate the mechanism responsible for the increase of S100B and the possible association with long term cognitive impairment.

Comparing mortality in renal patients on hemodialysis versus peritoneal dialysis using a marginal structural model.

When comparing the causal effect of peritoneal dialysis (PD) and hemodialysis (HD) treatment on lowering mortality in renal patients, using observational data, it is necessary to adjust for different forms of confounding and informative censoring. Both the type of dialysis treatment that is started with and mortality are affected by baseline covariates. Longitudinal and baseline variables can affect both the probability of switching from one type of dialysis to the other, and mortality. Longitudinal and baseline variables can also affect the probability of receiving a kidney transplant, possibly causing informative censoring. Adjusting for longitudinal variables by including them as covariates in a regression model potentially causes bias, for instance by losing a possible indirect effect of dialysis on mortality via these longitudinal variables. Instead, we fitted a marginal structural model (MSM) to estimate the causal effect of dialysis type, adjusted for confounding and informative censoring. We used the MSM to compare the hazard of death as well as cumulative survival between the potential treatment trajectories "always PD" and "always HD" over time, conditional on age and diabetes mellitus status. We used inverse probability weighting (IPW) to fit the MSM.