Assessment of factual recall and higher-order cognitive domains in an open-book medical school examination.

Open-book examinations (OBEs) will likely become increasingly important assessment tools. We investigated how access to open-book resources affected questions testing factual recall, which might be easy to look-up, versus questions testing higher-order cognitive domains. Few studies have investigated OBEs using modern Internet resources or as summative assessments. We compared performance on an examination conducted as a traditional closed-book exam (CBE) in 2019 (N = 320) and a remote OBE with free access to Internet resources in 2020 (N = 337) due to COVID-19. This summative, end-of-year assessment focused on basic science for second-year medical students. We categorized questions by Bloom's taxonomy ('Remember', versus 'Understand/Apply'). We predicted higher performance on the OBE, driven by higher performance on 'Remember' questions. We used an item-centric analysis by using performance per item over all examinees as the outcome variable in logistic regression, with terms 'Open-Book, 'Bloom Category' and their interaction. Performance was higher on OBE questions than CBE questions (OR 2.2, 95% CI: 2.14-2.39), and higher on 'Remember' than 'Understand/Apply' questions (OR 1.13, 95% CI: 1.09-1.19). The difference in performance between 'Remember' and 'Understand/Apply' questions was greater in the OBE than the CBE ('Open-Book' * 'Bloom Category' interaction: OR 1.2, 95% CI: 1.19-1.37). Access to open-book resources had a greater effect on performance on factual recall questions than higher-order questions, though performance was higher in the OBE overall. OBE design must consider how searching for information affects performance, particularly on questions measuring different domains of knowledge.

Mechanical Ventilation and Extracorporeal Membrane Oxygenation as a Bridging Strategy to Lung Transplantation: Significant Gains in Survival.

Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are increasingly used to bridge patients to lung transplantation. We investigated the impact of using MV, with or without ECMO, before lung transplantation on survival after transplantation by performing a retrospective analysis of 826 patients who underwent transplantation at our high-volume center. Recipient characteristics and posttransplant outcomes were analyzed. Most lung transplant recipients (729 patients) did not require bridging; 194 of these patients were propensity matched with patients who were bridged using MV alone (48 patients) or MV and ECMO (49 patients). There was no difference in overall survival between the MV and MV+ECMO groups (p = 0.07). The MV+ECMO group had significantly higher survival conditioned on surviving to 1 year (median 1,811 days ([MV] vs. not reached ([MV+ECMO], p = 0.01). Recipients in the MV+ECMO group, however, were more likely to require ECMO after lung transplantation (16.7% MV vs. 57.1% MV+ECMO, p < 0.001). There were no differences in duration of postoperative MV, hospital stay, graft survival, or the incidence of acute rejection, renal failure, bleeding requiring reoperation, or airway complications. In this contemporary series, the combination of MV and ECMO was a viable bridging strategy to lung transplantation that led to acceptable patient outcomes.

Proteasome Inhibitor Carfilzomib-Based Therapy for Antibody-Mediated Rejection of the Pulmonary Allograft: Use and Short-Term Findings.

We present this observational study of lung transplant recipients (LTR) treated with carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if complement-1q (C1q)-fixing ability of their immunodominant (ID) donor-specific anti-human leukocyte antibody (DSA) was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG mean fluorescence intensity (MFI) fell from 7664 (IQR 3230-11 874) to 1878 (653-7791) after therapy (p = 0.001) and to 1400 (850-8287) 2 weeks later (p = 0.001). DSA C1q MFI fell from 3596 (IQR 714-14 405) to <30 after therapy (p = 0.01) and <30 2 weeks later (p = 0.02). Forced expiratory volume in 1s ( FEV1 ) fell from mean 2.11 L pre-AMR to 1.92 L at AMR (p = 0.04). FEV1 was unchanged after CFZ (1.91 L) and subsequently rose to a maximum of 2.13 L (p = 0.01). Mean forced expiratory flow during mid forced vital capacity (25-75) (FEF25-75 ) fell from mean 2.5 L pre-AMR to 1.95 L at AMR (p = 0.01). FEF25-75 rose after CFZ to 2.54 L and reached a maximum of 2.91 L (p = 0.01). Responders had less chronic lung allograft dysfunction or progression versus nonresponders (25% vs. 83%, p = 0.04). No deaths occurred within 120 days and 7 patients died post CFZ therapy of allograft failure. Larger prospective interventional studies are needed to further describe the benefit of CFZ-based therapy for pulmonary AMR.

Effectiveness of continuous or intermittent vital signs monitoring in preventing adverse events on general wards: a systematic review and meta-analysis.

BACKGROUND: Vital signs monitoring is an old hospital practice for patient safety but evaluation of its effectiveness is not widespread. We aimed to identify strategies to improve intermittent or continuous vital signs monitoring in general wards; and their effectiveness in preventing adverse events on general hospital wards. METHODS: Publications searched between 1980 and June 2014 in five databases. Main outcome measures were in-hospital death, cardiac arrest, intensive care unit (ICU) transfers, length of stay, identification of physiological deterioration and activation of rapid response systems. RESULTS: Twenty-two studies assessing the effect of continuous (9) or intermittent monitoring (13) and reporting outcomes on 203,407 patients in-hospital wards across 13 countries were included in this review. Both monitoring practices led to early identification of patient deterioration, increased rapid response activations and improvements in timeliness or completeness of vital signs documentation. Innovative intermittent monitoring approaches are associated with modest reduction in in-hospital mortality over intermittent vital signs monitoring in 'usual care'. However, there was no evidence of significant reduction in ICU transfers or other adverse events with either intermittent or continuous monitoring. CONCLUSIONS: This review of heterogeneous monitoring approaches found no conclusive confirmation of improvements in prevention of cardiac arrest, reduction in length of hospital stay, or prevention of other neurological or cardiovascular adverse events. The evidence found to date is insufficient to recommend continuous vital signs monitoring in general wards as routine practice. Future evaluations of effectiveness need to be undertaken with more rigorous methods and homogeneous outcome measurements.

Non-beneficial treatments in hospital at the end of life: a systematic review on extent of the problem.

PURPOSE: To investigate the extent of objective 'non-beneficial treatments (NBTs)' (too much) anytime in the last 6 months of life in routine hospital care. DATA SOURCES: English language publications in Medline, EMBASE, PubMed, Cochrane library, and the grey literature (January 1995-April 2015). STUDY SELECTION: All study types assessing objective dimensions of non-beneficial medical or surgical diagnostic, therapeutic or non-palliative procedures administered to older adults at the end of life (EOL). DATA EXTRACTION: A 13-item quality score estimated independently by two authors. RESULTS OF DATA SYNTHESIS: Evidence from 38 studies indicates that on average 33-38% of patients near the EOL received NBTs. Mean prevalence of resuscitation attempts for advanced stage patients was 28% (range 11-90%). Mean death in intensive care unit (ICU) was 42% (range 11-90%); and mean death rate in a hospital ward was 44.5% (range 29-60%). Mean prevalence of active measures including dialysis, radiotherapy, transfusions and life support treatment to terminal patient was 7-77% (mean 30%). Non-beneficial administration of antibiotics, cardiovascular, digestive and endocrine treatments to dying patients occurred in 11-75% (mean 38%). Non-beneficial tests were performed on 33-50% of patients with do-not-resuscitate orders. From meta-analyses, the pooled prevalence of non-beneficial ICU admission was 10% (95% CI 0-33%); for chemotherapy in the last six weeks of life was 33% (95% CI 24-41%). CONCLUSION: This review has confirmed widespread use of NBTs at the EOL in acute hospitals. While a certain level of NBT is inevitable, its extent, variation and justification need further scrutiny.

Relationship of Normalized Protein Catabolic Rate with Nutrition Status and Long-Term Survival in Peritoneal Dialysis Patients.

The normalized protein catabolic rate (nPCR) reflects daily dietary protein intake in stable dialysis patients. In peritoneal dialysis (PD) patients, reports about the importance of nPCR as marker of nutrition and outcome have been inconsistent. The objective of the present study was to investigate the relationships of nPCR with body composition parameters, micronutrient electrolytes, and long-term survival in PD patients. From November 2000 to May 2008, 57 PD patients were enrolled in the study. On enrollment, demographic, clinical, and biochemical data were recorded. Patients were followed through September 2011. Mean age of the patients was 56 years, and 61% were of African descent. Mean and maximum follow-up were 2.83 years and 11 years respectively. Mean daily nPCR was 0.944 g/kg. The nPCR correlated directly with albumin (r = 0.34, p = 0.012), magnesium (r = 0.48, p < 0.0001), phosphorus (r = 0.42, p = 0.02), and the phase angle body composition parameter (r = 0.26, p = 0.049). Compared with patients whose enrollment daily nPCR was less than 0.8 g/kg, those with an enrollment daily nPCR of 0.8 g/kg or more experienced significantly better 11-year cumulative survival (p = 0.04). In multivariate Cox regression analysis with adjustment for confounding variables, nPCR was an independent predictor of all-cause mortality (p = 0.018). In conclusion, lower nPCR is associated with poorer nutrition status and increased risk of all-cause mortality in PD patients followed for up to 11 years.

Serum magnesium concentration is a significant predictor of mortality in peritoneal dialysis patients.

We previously reported that lower serum magnesium is associated with poorer nutrition status, impaired cellular health, and increased inflammation in peritoneal dialysis (PD) patients. The present study was designed to investigate the prognostic value of serum magnesium for mortality in PD patients. From November 2000 to July 2008, the study enrolled 62 patients, recording their demographic, clinical, and biochemical data. Patients were followed to September 2011. Mean age of the patients was 55 +/- 16 years, and in this cohort, 55% were women, 63% were African American, and 25% had diabetes. Mean serum magnesium was 1.597 +/- 0.28 mEq/L. Maximum follow-up was 10.8 years. During the follow-up period, 27 patients died (43.5%). Serum magnesium was significantly higher in the patients who survived than in those who did not (1.757 mEq/L vs. 1.515 mEq/L, p = 0.04). Patients were then stratified by enrollment magnesium. After 10.8 years of observation, cumulative survival was significantly better in patients with an enrollment serum magnesium greater than 1.6 mEq/L than in patients with an enrollment serum magnesium of 1.6 mEq/L or less (p = 0.04). Multivariate Cox regression analysis revealed that serum magnesium is a significant predictor of mortality (relative risk: 0.984; p = 0.048) after adjusting for age, race, sex, diabetes, and months on dialysis at enrollment. In conclusion, lower serum magnesium is a significant predictor of higher mortality in PD patients. Factors affecting the serum magnesium concentration in PD patients should be investigated in more detail.

Relationship between alkaline phosphatase and all-cause mortality in peritoneal dialysis patients.

Elevated levels of serum alkaline phosphatase (AlkPhos) have been reported to be associated with increased mortality risk in hemodialysis (HD) patients. We examined the association of serum AlkPhos with all-cause mortality in our PD patients. The study enrolled 90 PD patients beginning in 1995. On enrollment, demographics and clinical and biochemical data were recorded. Patients were followed to September 2011. Mean age of the enrollees was 52 years, with 61% being women, and most (81%) being of African descent. Mean and median AlkPhos were 135 U/L and 113 U/L respectively. Mean and maximum follow-up were 2.61 and 16 years respectively. As expected, AlkPhos correlated directly with serum intact parathyroid hormone (r = 0.36, p = 0.003). In a Cox multivariate regression analysis with adjustment for confounding variables, AlkPhos as a continuous (relative risk: 1.016; p = 0.004) anda categorical variable [> 120 U/L and < or = 120 U/L (relative risk: 6.0; p = 0.03)] remained a significant independent predictor of mortality. For each unit increase in enrollment AlkPhos, there was a 1.6% increase in the relative risk of death. Elevated serum AlkPhos is significantly and independently associated with increased mortality risk in our PD patients followed for up to 16 years. AlkPhos should be evaluated prospectively as a potential therapeutic target in clinical practice.

Dialysis vintage, body composition, and survival in peritoneal dialysis patients.

The relationship between dialysis vintage (length of time on dialysis), body composition, and survival has been reported in hemodialysis patients. In the present study, we examined the association ofdialysis vintage with body composition and survival in peritoneal dialysis (PD) patients. At enrollment, body composition in 65 PD patients was determined by bioelectrical impedance analysis. Patients (mean age at enrollment: 54 years) were followed for up to 11 years maximum. At enrollment, the mean, median, and maximum dialysis vintages were 51, 34, and 261 months respectively. After adjusting for age, race, sex, and diabetes status, dialysis vintage was indirectly correlated (partial correlation coefficients) with body weight (r = -0.40, p = 0.001), body mass index (r = -0.40, p = 0.002), body surface area (r = -0.39, p = 0.002), body cell mass (r = -0.39, p = 0.002), total body fat weight (r = -0.30, p = 0.02), and fat percentage of body weight (r = -0.31, p = 0.018), and directly correlated with extracellular mass to body cell mass ratio (r = 0.27, p = 0.039). The observed cumulative survival was significantly higher (p = 0.007) in patients with a dialysis vintage at enrollment of 35 months or less, than in patients with dialysis vintage at enrollment of more than 35 months. In the multivariate Cox regression analysis, adjusting for age, race, sex, and diabetes, dialysis vintage at enrollment remained an independent predictor of mortality (relative risk: 1.010; p = 0.002). Increase in relative risk of death with increasing dialysis vintage may be partly explained by the association of vintage with unfavorable changes in body composition and the nutrition status of patients over time.

Changes in brain morphology in patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure. METHODS: 60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template. RESULTS: Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p<0.05, corrected for topological false discovery rate across the entire brain). A reduction in grey matter was also seen within the cerebellum, maximal in the left lobe VIIIb close to XI, extending across the midline into the right lobe. CONCLUSION: These data show that OSA is associated with focal loss of grey matter that could contribute to cognitive decline. Specifically, lesions in the cerebellum may result in both motor dysfunction and working memory deficits, with downstream negative consequences on tasks such as driving.

Treatment of secondary hyperparathyroidism in ESRD: a 2-year, single-center crossover study.

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease. The management of SHPT commonly involves vitamin D, either calcitriol or newer analogs (paricalcitol or doxercalciferol), along with dietary phosphorus restriction and phosphate binding agents. Published reports have suggested that treatment with paricalcitol in hemodialyzed (HD) patients offers a morbidity or mortality advantage in comparison with treatment with calcitriol. We have recently reported that switching from calcitriol to paricalcitol resulted in a lower serum calcium and calcium-phosphorus product (Ca x P product), as well as lower parathyroid hormone (PTH) and alkaline phosphatase during 6 months of serial treatment. We converted all HD patients in our large urban dialysis center from calcitriol to paricalcitol using a 1:3 conversion ratio, on the basis of published data. Comparisons of individual patient mean biochemical values, as well as episodes of hypercalcemia and elevated Ca x P product, were made after adjusting for equivalent doses. In addition, we recorded the number of missed doses during two years of therapy. No patient in this study had received a calcimimetic before or during the study period. Fifty-nine patients were treated with calcitriol for at least 12 months and then completed 12 months of paricalcitol. Conversion from calcitriol to paricalcitol resulted in lower serum calcium (P=0.0003), lower serum phosphorus (P=0.027), lower Ca x P product (P=0.003), reduced PTH (P=0.001) and reduced serum alkaline phosphatase (P=0.0005). Most dramatically, there was a highly significant difference in the number of missed doses (P<0.0001) during the treatments. This 2-year single-center study, comparing long-term calcitriol with paricalcitol treatment in the same HD patients, extends our previous findings, offers new information regarding single episodes of potentially adverse biochemical effects related to vitamin D therapy, and provides several clues that may explain the outcome advantages suggested by previously published retrospective analyses of large dialysis provider-pooled databases.

Extracellular mass/body cell mass ratio is an independent predictor of survival in peritoneal dialysis patients.

Malnutrition is a strong predictor of mortality in peritoneal dialysis (PD) patients. Extracellular mass (ECM) contains all the metabolically inactive, whereas body cell mass (BCM) contains all the metabolically active, tissues of the body. ECM/BCM ratio is a highly sensitive index of malnutrition. The objective of this study was to explore the relationship between ECM/BCM ratio and survival in PD patients. We enrolled 62 patients from November 2000 to July 2008. On enrollment, demographic, clinical, and biochemical data were recorded. Bioimpedance analysis (BIA) was used to determine ECM and BCM in PD patients. Patients were followed up to November 2008. Mean age was 54+/-16 (s.d.) years; female, 55%; African Americans, 65%; diabetic, 24%. Mean ECM/BCM ratio was 1.206+/-0.197 (range: 0.73-1.62). Diabetics had higher ECM/BCM ratio than nondiabetics (1.29 vs 1.18, P=0.04). ECM/BCM ratio correlated directly with age (r=0.38, P=0.002) and inversely with serum albumin (r=-0.43, P=0.001), creatinine (-0.24, P=0.08), blood urea nitrogen (r=-0.26, P=0.06), and total protein (r=-0.31, P=0.026). Using multivariate Cox regression analysis, adjusting for age, race, gender, diabetes, and human immunodeficiency virus status, enrollment ECM/BCM ratio was a significant independent predictor of mortality (relative risk=1.035, P=0.018). For every 10% increase in the ECM/BCM ratio, the relative risk of death was increased by about 35%. In conclusion, BIA-derived enrollment ECM/BCM ratio, a marker of malnutrition, was an independent predictor of long-term survival in PD patients.

Serum fructosamine versus glycosylated hemoglobin as an index of glycemic control, hospitalization, and infection in diabetic hemodialysis patients.

Diabetes is the most common cause of end-stage renal disease and an important risk factor for morbidity and mortality in dialysis patients. Glycemic control, utilizing serial measurement of glycosylated hemoglobin (HbA1c), is generally recommended to limit end-organ damage, including cardiovascular morbidity and mortality. We, along with others, have previously suggested that HbA1c may not be a reliable measure of glycemic control in dialysis patients, and have therefore explored the use of serum fructosamine (SF) as an alternative marker. The objective of this study was to compare HbA1c levels with SF in monitoring glycemic control and associated morbidity (infection and hospitalization) in diabetic patients in a large urban hemodialysis (HD) center. We enrolled 100 diabetic HD patients and followed them up prospectively for 3 years. Data on demographics, as well as biochemical and clinical data, including hospitalizations and infections, were recorded. The mean age was 63 years. In all 54% were women and the majority were African Americans (72%). As expected, HbA1c and albumin-corrected fructosamine (AlbF) levels were highly correlated and both were significantly associated with serum glucose. AlbF, however, was more highly correlated with mean glucose values when less than 150 mg/dl and was a more useful predictor of morbidity. By univariate logistic regression and by Poisson regression analysis, AlbF, but not HbA1c, was a significant predictor of hospitalization. Additionally, in patients dialyzed by arteriovenous (AV) access (that is, excluding those dialyzed via vascular catheters), AlbF, but not HbA1c, was a significant predictor of infection. In conclusion, AlbF is as reliable a marker as HbA1c for glycemic control in diabetic patients on HD, and may be advantageous for patients with serum glucose in a desirable therapeutic range (<150 mg/dl). In addition, AlbF, but not HbA1c, is associated with morbidity (hospitalizations and infections) in diabetic patients on HD.

Relationship of serum magnesium to body composition and inflammation in peritoneal dialysis patients.

Magnesium is one of the most abundant cations in the body and is involved in many cell functions. Serum magnesium concentration is maintained within a narrow range by the kidney and digestive tract. It has been reported that a lower serum magnesium level is a significant predictor for mortality in hemodialysis patients. Body composition and inflammation are important predictors of mortality in peritoneal dialysis (PD) patients. The objective of the present study was to examine the relationship of serum magnesium with body composition and inflammation in PD patients. Our study enrolled 62 PD patients treated at the Long Island College Hospital between November 2000 and July 2008. Demographic, clinical, and biochemical data were recorded. Body composition parameters were determined by bioelectrical impedance analysis (BIA). High sensitivity C-reactive protein (hs-CRP), a marker of inflammation was measured by the immunoturbidimetric method. In these patients (mean age: 55 years; 63% African American; 55% women; 25% with diabetes), the mean (+/- standard deviation) serum magnesium and hs-CRP were 1.597 +/- 0.28 mEq/L and 13.70 +/- 21 mg/L respectively. Serum magnesium was directly correlated with serum markers of nutrition: albumin (r = 0.42, p = 0.001), creatinine (r = 0.43, p = 0.0001), and total protein (r = 0.44, p < 0.0001). Serum magnesium was also directly correlated with phase angle, a BIA parameter and marker of cellular health (correlation coefficient: r = 0.35; p = 0.006), and inversely correlated with the extracellular mass/body cell mass ratio (r = -0.34, p = 0.008), a highly sensitive marker of malnutrition. We observed an inverse correlation between serum magnesium and hs-CRP (r = -0.37, p = 0.02) in PD patients. In conclusion, lower serum magnesium is associated with poorer nutrition status, deteriorating cellular health, and increased inflammation, which may contribute to the increased risk of mortality in PD patients.

Autotitrating versus standard noninvasive ventilation: a randomised crossover trial.

The aim of the present study was to compare the efficacy of automatic titration of noninvasive ventilation (NIV) with conventional NIV in stable neuromuscular and chest wall disorder patients established on long-term ventilatory support. In total, 20 neuromuscular and chest wall disease patients with nocturnal hypoventilation treated with long-term NIV completed a randomised crossover trial comparing two noninvasive pressure support ventilators: a standard bilevel ventilator (VPAP III) and a novel autotitrating bilevel ventilator (AutoVPAP). Baseline physiological measurements, overnight polysomnography and Holter monitoring were repeated at the end of each 1-month treatment period. Nocturnal oxygenation was comparable between the autotitrating device and standard ventilator, as were sleep efficiency, arousals and heart rate variability. However, there was a small significant increase in mean overnight transcutaneous carbon dioxide tension (median (interquartile range) 7.2 (6.7-7.7) versus 6.7 (6.1-7.0) kPa) and a decrease in percentage stage 1 sleep (mean+/-sd 16+/-9 versus 19+/-10%) on autotitrating NIV compared with conventional NIV. Autotitrating noninvasive ventilation using AutoVPAP produced comparable control of nocturnal oxygenation to standard nonivasive ventilation, without compromising sleep quality in stable neuromuscular and chest wall disease patients requiring long-term ventilatory support for nocturnal hypoventilation.

Clinical outcomes of solid organ transplant recipients with ehrlichiosis.

Because of our experience with severe Ehrlichia infections in lung transplant recipients, we reviewed all cases of ehrlichiosis in solid organ transplant recipients at Barnes-Jewish Hospital in St. Louis, Missouri. Between 1996 and 2007, 25 cases of ehrlichiosis were identified. We retrospectively collected demographic, clinical, laboratory, and outcomes data, and we compared the 5 cases in lung transplant recipients with 20 cases in other solid organ transplant recipients (heart, 2; kidney, 13; liver, 5). The presenting symptoms in the majority of both groups consisted of fever and headache. Clinical outcomes were worse in the lung transplant group and included a greater need for intensive care unit treatment (80% vs. 20%, P=0.02), longer length of hospital stay (21 vs. 5 days, P=0.02), and propensity to develop acute lung injury or acute respiratory distress syndrome (60% vs. 10%, P=0.04). No mortalities occurred in either group of patients. In an endemic area, ehrlichiosis is not unusual in solid organ transplant recipients, and lung transplant recipients tend to have a more severe illness.

Enrollment fluid status is independently associated with long-term survival of peritoneal dialysis patients.

Fluid overload is a common complication in peritoneal dialysis (PD) patients. The prognostic importance of enrollment fluid status in long-term PD patients remains to be investigated. The objective of the present study was to investigate the prognostic importance of enrollment fluid status in the long-term survival of PD patients. We enrolled 53 PD patients (mean age: 53 years) from November 2000 to February 2006. On enrollment, demographic, clinical, and biochemical data were recorded. Bioelectrical impedance analysis (BIA) was used to determine the fluid status of PD patients, including extracellular water (ECW), intracellular water (ICW), and total body water (TBW). Fluid status was corrected for body surface area (BSA): ECW-BSA, ICW-BSA, and TBW-BSA respectively. Patients were followed to January 2008. The ECW-BSA correlated negatively with albumin, a marker of nutrition (r = -0.53, p < 0.0001). The ICW/ECW ratio (r = 0.36, p = 0.018) correlated directly and the ECW/ TBW ratio (r = -0.36, p = 0.019) correlated negatively with creatinine. Patients who survived during the study period had a significantly lower ECW-BSA (8.29 L/m2 vs. 9.91 L/m2, p = 0.001) than did those who did not survive. Patients with enrollment ECW-BSA below 9 L/m2 had a significantly better 7-year cumulative survival (Kaplan-Meier) than did patients with a ECW-BSA of 9 L/m2 or more (p = 0.019). Using multivariate Cox regression analysis, adjusting for age, race, diabetes, human immunodeficiency virus (HIV) status, and months on dialysis at enrollment, ECW-BSA was a significant independent predictor of mortality (relative risk: 1.50; p = 0.03). In conclusion, ECW-BSA was a significant independent predictor of long-term survival in PD patients.

Obstructive sleep apnoea and Alzheimer's disease: In search of shared pathomechanisms.

Alzheimer's disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments. Based on the body of data, we here suggest that excessive and prolonged neuronal activity might contribute to genesis and acceleration of both AD and OSA in the absence of appropriately structured sleep. Further, we argue that external factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain, and further promote disease progression. If this hypothesis is proven in future studies, it could have far-reaching clinical translational implications, as well as implications for future treatment strategies in OSA.

Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

BACKGROUND: Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. METHODS: Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. RESULTS: Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. CONCLUSIONS: Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.