Healthcare Intensity at Initiation of Chronic Dialysis among Older Adults

Little is known about the circumstances under which older adults initiate chronic dialysis and subsequent outcomes. Using national registry data, we conducted a retrospective analysis of 416,657 Medicare beneficiaries aged ≥67 years who initiated chronic dialysis between January 1995 and December 2008. Our goal was to define the relationship between health care intensity around the time of dialysis initiation and subsequent survival and patterns of hospitalization, use of intensive procedures (mechanical ventilation, feeding tube placement, and cardiopulmonary resuscitation), and discontinuation of dialysis before death. We found that most patients (64.5%) initiated dialysis in the hospital, including 36.6% who were hospitalized for ≥2 weeks and 7.4% who underwent one or more intensive procedures. Compared with patients who initiated dialysis in the outpatient setting, those who received the highest intensity of care at dialysis initiation (those hospitalized ≥2 weeks and receiving at least one intensive procedure) had a shorter median survival (0.7 versus 2.1 years; P<0.001), spent a greater percentage of remaining follow-up time in the hospital (median, 22.9% versus 3.1%; P<0.001), were more likely to undergo subsequent intensive procedures (44.9% versus 26.0%; adjusted hazard ratio, 2.33; 95% confidence interval [CI], 2.27 to 2.39), and were less likely to have discontinued dialysis before death (19.1% versus 26.2%; adjusted odds ratio, 0.68; 95% CI, 0.65 to 0.72). In conclusion, most older adults initiate chronic dialysis in the hospital. Those who have a prolonged hospital stay and receive other forms of life support around the time of dialysis initiation have limited survival and more intensive patterns of subsequent healthcare utilization.Over the last decade, a growing number of older adults are initiating chronic dialysis.¹ Survival among these older patients is extremely limited,^2,3 and many experience functional decline,^4,5 frequent hospitalization,⁶ and a high symptom burden⁷ after initiation of chronic dialysis. In this setting, patients must often make trade-offs between interventions intended to lengthen life and those directed at other treatment goals, such as maximizing quality of life and maintaining independence.Rates of hospitalization and use of intensive procedures, such as mechanical ventilation, feeding tube placement, and cardiopulmonary resuscitation (CPR), at the end of life are exceptionally high in older dialysis patients compared with other older Medicare beneficiaries with life-limiting illness.⁸ Discussions about prognosis, goals, and preferences are often lacking, and patients may have little appreciation of their likelihood of clinical deterioration or knowledge of more conservative alternatives, such as hospice.⁹ Uncertainty about disease trajectory and prognosis can hamper formulation of future plans and treatment preferences.^10–12Prior studies have evaluated the association of patient characteristics (e.g., comorbid conditions and functional status)^5,13,14 and treatment practices (e.g., early nephrology referral and type of vascular access)^15,16 before and at the time of dialysis initiation with subsequent outcomes. However, many of these analyses did not capture information on clinical circumstances around the time of dialysis initiation. In reality, chronic dialysis is often initiated in the context of acute illness^17,18 and rapid or unexpected loss of renal function.¹⁴We hypothesized that illness severity around the time of dialysis initiation—as reflected in measures of health care intensity, such as length of hospitalization and use of intensive procedures—might provide information useful for anticipatory guidance and supporting treatment decisions in older adults newly initiated on chronic dialysis. To evaluate this hypothesis, we used data from the U.S. Renal Data System (USRDS), a national registry of ESRD, to identify 416,657 Medicare beneficiaries aged ≥67 years and describe the intensity of care they experienced around the time of initiation of chronic dialysis and its association with survival and patterns of future healthcare utilization.     

Bronchoscopic performance of bronchoalveolar lavage in germany – a call for standardization

Background:Bronchoalveolar lavage (BAL) is a widely used clinical tool in diagnosing interstitial lung diseases. Although there are recommendations and guidelines, the procedure is not completely standardized. Varying approaches likely influence the conclusiveness of BAL data and may be one reason for the divergent judgement of their value between different centers.Objectives:To evaluate how BAL is performed in Germany using an electronically based survey.Methods:We conducted a cross-sectional online survey among all members of the German Respiratory Society.Results:608 members responded to the survey and of these 500 perform lavages. Most bronchoscopists (344/500) do not use a tube and have no anesthesiologist present during the procedure (405/500). Propofol is used by 76.8% and midazolam by 67.9% (n = 405), often in combination. A major difference was noted regarding the total volume of instillation. Many respondents use a predefined fixed amount of instilled volume (202/500), whereas an almost equal number use variable volumes based on the recovery (196/500). The minimum recovery volume predefined by 217/499 ranged from 3-150 ml (median 30 ml; mean 42.2 ± 55.1 ml). Most respondents did not transport their samples in special medium (61.5%) or on ice (72.8%). The average time between recovery and arrival at the lab was 115.6±267.0 min (n = 323).Conclusion:This study shows the broad spectrum of variations in the performance of BAL in Germany, which could have a negative effect on the method’s clinical value. There is a need for training and standardization of BAL performance.     

Oligonucleotide-protamine-albumin nanoparticles: Protamine sulfate causes drastic size reduction.

Nanoparticles prepared by self-assembly from oligonucleotides (ONs), protamine free base, and human serum albumin ("ternary proticles") are spheres of diameters around 200 nm. Substitution of the protamine free base by protamine sulfate leads to proticles of only around 40 nm in diameter with otherwise unchanged properties. The availability of drug delivery systems of very similar composition but grossly different size may be advantageous when dealing with cells which show size-dependent particle uptake. These nanoparticles are promising candidates for ON delivery to cells because of the following reasons: (1) They are stable for several hours in solutions of up to physiological ionic strength; (2) they are efficiently taken up by cells; (3) after cellular uptake, they easily release the ONs even when these are present as phosphorothioates.     

Body distribution of azidothymidine bound to hexyl-cyanoacrylate nanoparticles after i.v. injection to rats

Cells of the reticuloendothelial system (RES e.g. macrophages) play an important role in the immunopathogenesis of AIDS. The objective of the present study was to investigate the possibility of specifically targeting antiviral drugs such as azidothymidine (AZT) to macrophages using nanoparticles as colloidal drug carriers. In a first series of experiments the body distribution of

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–labelled AZT bound to nanoparticles and a similarly prepared control solution with unbound AZT were studied in rats after intravenous injection. In a second series of experiments polysorbate 80-coated nanoparticles and a solution of AZT in saline were tested.

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–labelled AZT was bound to nanoparticles using the surfactant bis(2-ethylhexyl) sulphosuccinate sodium (DOSS). The radioactivity in several organs, including those containing large numbers of macrophages, was measured after intravenous injection of the AZT-nanoparticles and the AZT-control solutions. AZT concentrations were up to 18 times higher in organs belonging to the RES if the drug was bound to nanoparticles compared with unbound AZT. These results demonstrate that nanoparticles are a potential drug targeting system for anti-AIDS drugs. The increase in drug concentration at the sites containing abundant macrophages may allow a reduction in dosage to reduce systemic toxicity.     

HPV16 activates the AIM2 inflammasome in keratinocytes

Human papillomaviruses (HPV) are double-stranded DNA viruses, which selectively infect keratinocytes in stratified epithelia. After an initial infection, many patients clear HPV. In some patients, however, HPV persist, and dysfunctional innate immune responses to HPV infection could be involved in the ineffective clearing of these viruses. In this study, the mechanisms of HPV-induced immune responses in keratinocytes were investigated. Binding of viral DNA leads to AIM2 inflammasome activation and IL-1β release, while IFI16 activation results in IFN-β release. Using immunohistochemistry, AIM2 and IFI16—two recently identified sensors for cytosolic DNA—were also detected in HPV positive skin lesions. CISH stainings further confirmed the presence of cytosolic HPV16 DNA in biopsy samples. Moreover, active IL-1β and cleaved caspase-1 were detected in HPV infected skin, suggesting inflammasome activation by viral DNA. In subsequent functional studies, HPV16 DNA triggered IL-1β and IL-18 release via the AIM2 inflammasome in normal human keratinocytes. Although HPV DNA did not induce IFN-β in keratinocytes, IFN-β secretion was observed when AIM2 was blocked. Meanwhile, blocking of IFI16 increased HPV16 DNA-induced IL-1β, but not IL-18, secretion. These findings suggest crosstalk between IFI16 and AIM2 in the immune response to HPV DNA. In sum, novel aspects concerning HPV-induced innate immune responses were identified. Eventually, understanding the mechanisms of HPV-induced inflammasome activation could lead to the development of novel strategies for the prevention and treatment of HPV infections.     

Fear of falling,balance, and gait velocity in patients with stroke

After a stroke balance can be impaired, that may influence the physical activities which can be undertaken. A person's confidence in performing activities without falling could be as important as the real balance ability in situations of daily living. The aims of the study were to evaluate the relationship between perceived self-confidence in task performance without falling, using the Falls Efficacy Scale, Swedish version, (FES(S)) and observer-assessed balance, measured by the BDL Balance Scale (BDL BS) and also between the FES(S) and gait velocity. Thirty-one subjects with stroke, 32–62 years of age, time since onset between 3 and 104 months, participated. The FES(S) was significantly correlated with the BDL BS (r = 0.49, p = 0.008). Furthermore there were significant correlations between the FES(S) and self-selected (r = 0.53, p = 0.003) as well as for maximum (r = 0.55, p = 0.002) gait velocity. The results indicate that the use of the FES(S) can be recommended in subjects with stroke and balance deficit in order to map out the dimension of self-confidence in balance problems. However, in more highly functioning subjects with stroke other fall-efficacy assessments with major demands on balance performance may be preferable due to partly ceiling effect in the study population.     

Outcomes of plasma exchange in patients with transplant‐associated thrombotic microangiopathy based on time of presentation since transplant

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA‐TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA‐TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA‐TMA since transplant. Thirty‐three patients diagnosed with TA‐TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All‐cause day‐30 and day‐100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P‐value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30‐day and 100‐day all‐cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P‐value = 0.25 and 0.08, for 30‐ and 100‐day all‐cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA‐TMA. The overall efficacy of PE is poor; however, patients who present with TA‐TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis 30:147–153, 2015. © 2014 Wiley Periodicals, Inc.