Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.

Codon-Optimized and de novo-Synthesized E-Selectin/AAV2 Dose-Response Study for Vascular Regeneration Gene Therapy.

OBJECTIVE: This study focuses on dose-response investigation using a codon-optimized and de novo-synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies. BACKGROUND: Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug-enabling studies. METHODS: Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 10 9 VG to 2 × 10 11 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed. RESULTS: Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 10 11 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied. CONCLUSIONS: E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 10 11 VG aliquots injected intramuscularly.

Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.

Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.

Clinical burden of invasive Escherichia coli disease among older adult patients treated in hospitals in the United States.

BACKGROUND: Invasive extraintestinal pathogenic Escherichia coli disease (IED) can lead to severe outcomes, particularly among older adults. However, the clinical burden of IED in the U.S. has not been well characterized. METHODS: IED encounters among patients ≥ 60 years old were identified using the PINC AI™ Healthcare Database (10/01/2015-03/31/2020) by either a positive E. coli culture in blood or another normally sterile body site and ≥ 1 sign of systemic inflammatory response syndrome or signs of sepsis, or a positive E. coli culture in urine with urinary tract infection and signs of sepsis. Medical resource utilization, clinical outcomes, and E. coli isolate characteristics were descriptively reported during the first IED encounter and during the following year (observation period). RESULTS: Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 78.5% with signs of sepsis). Most encounters involved community-onset IED (94.3%) and required hospitalization (96.5%; mean duration: 6.9 days), with 32.4% of patients being admitted to the intensive care unit (mean duration: 3.7 days). Most E. coli isolates were resistant to ≥ 1 antibiotic category (61.7%) and 34.4% were resistant to ≥ 3 antibiotic categories. Following their first IED encounter, 34.8% of patients were transferred to a skilled nursing/intermediate care facility, whereas 6.8% had died. During the observation period, 36.8% of patients were rehospitalized, 2.4% had IED recurrence, and in-hospital death increased to 10.9%. CONCLUSIONS: IED is associated with substantial clinical burden at first encounter with considerable long-term consequences. Findings demonstrate the need for increased IED awareness and highlight potential benefits of prevention.

Influence of allopurinol on thiopurine associated toxicity: A retrospective population-based cohort study.

AIMS: Thiopurines are important for treating inflammatory bowel disease, but are often discontinued due to adverse effects. Concomitant use of allopurinol might lower the risk of these unwanted effects, but large studies in the general population are lacking. The aims of this study were to evaluate rates of hepatotoxicity, myelotoxicity, pancreas toxicity and therapy persistence in adult thiopurine users with or without allopurinol. METHODS: A retrospective population-based cohort study was conducted within current thiopurine users (Clinical Practice Research Datalink). Among these patients, co-use of allopurinol was compared to non-use. Hazard ratios (HRs) for hepatotoxicity, myelotoxicity and pancreatitis were derived using time-dependent Cox proportional hazards models, and were adjusted for potential confounders. Persistence of thiopurine use was evaluated using Log-rank statistics. RESULTS: Patients using thiopurines (n = 37 360) were identified of which 1077 were concomitantly taking allopurinol. A 58% decreased risk of hepatotoxicity was observed in those concomitantly taking allopurinol (HR 0.42; 95% CI 0.30-0.60; NNT 46). Rate of myelotoxicity (HR 0.96; 95% CI 0.89-1.03) was not influenced. Risk of pancreatitis was increased (HR 3.00; 95% CI 1.01-8.93; NNH 337), but was only seen in those with active gout (suggesting confounding by indication). Finally, allopurinol co-users were able to maintain thiopurine therapy over twice as long as those not on allopurinol (3.9 years vs. 1.8 years, P < 0.0001). CONCLUSION: In thiopurine users, allopurinol is associated with a 58% reduced risk of hepatotoxicity. In addition, thiopurine persistence was prolonged by 2.1 years in allopurinol users. These data support the use of allopurinol in individuals requiring thiopurine therapy.

A simple nomogram for early postoperative risk prediction of clinically relevant pancreatic fistula after pancreatoduodenectomy.

PURPOSE: Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. METHODS: One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. RESULTS: Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. CONCLUSION: Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.

Prediction of Postoperative Visual Outcome in Patients with Idiopathic Epiretinal Membrane.

PURPOSE: The aim of this study was to estimate the association between preoperative characteristics in subjects with idiopathic epiretinal membrane (ERM) and visual acuity improvement after vitrectomy and create an algorithm for predicting postoperative visual outcome. METHODS: In a retrospective, cross-sectional study, we included adults with idiopathic ERM and excluded subjects with low-quality scans, other ocular conditions, and previous surgery except cataract surgery. Baseline characteristics were extracted from medical files, spectral-domain OCT, and OCT angiography. Visual improvement was expressed as a binary variable. RESULTS: Fifty-four subjects were included in the study. Three months postoperatively, 30 subjects improved, 10 remained stable, and 14 deteriorated. Spearman correlation showed no correlation between variables and visual acuity improvement (<0.39). Reduced dimensionality showed that baseline visual acuity, lens status, foveal aspect, spherical equivalent, and 2 interactive variables including foveal aspect and lens status have the strongest effect on improvement. Five-fold logistic regression based on these variables provided a model with AUC 0.9 ± 0.06. CONCLUSION: No variable has a direct predictive role on visual acuity improvement; however, baseline visual acuity, lens status, foveal aspect and spherical equivalent, when combined, provide a predictive model that could serve as a tool for more informed decisions.

The harmful-dysfunction account of disorder, individual versus social values, and the interpersonal variability of harm challenge.

This paper presents the interpersonal variability of harm challenge to Jerome Wakefield's harmful-dysfunction account (HDA) of disorder. This challenge stems from the seeming fact that what promotes well-being or is harmful to someone varies much more across individuals than what is intuitively healthy or disordered. This makes it at least prima facie difficult to see how judgments about health and disorder could, as harm-requiring accounts of disorder like the HDA maintain, be based on, or closely linked to, judgments about well-being and harm. This interpersonal variability of harm challenge is made salient by the difficulty faced by harm-requiring accounts of disorder in dealing satisfactorily with cases of intuitively disordered conditions that seem harmless because they do not deprive the individuals that they affect of anything that they value (e.g., desired infertility). I argue that this challenge is made more serious for the HDA by some clarifications Wakefield has recently made on harm. In recent publications, Wakefield dissociates himself from the sheer cultural-relativist view of harm attributed to him by some critics based on his linkage of harm to social values, and adopts a more qualified social-values-based view of harm that leaves room for criticism of the values endorsed by members of a cultural group at a given time. I show how Wakefield's qualified view makes it more difficult for the HDA to deal with the interpersonal variability of harm challenge, at least when applied to a Western cultural context where a high value is placed on autonomy and individual choice.

A semi-mechanistic model based on glutathione depletion to describe intra-individual reduction in busulfan clearance.

AIM: To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing. METHODS: Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a semi-mechanistic model and compare it to a previously developed empirical model. The latter included an empirically estimated time effect, where the semi-mechanistic model included theoretical glutathione depletion. As older age has been related to lower glutathione levels, this was tested as a covariate in the semi-mechanistic model. Lastly, a therapeutic drug monitoring (TDM) simulation was performed comparing the two models in target attainment. RESULTS: In both models, a similar clearance decrease of 7% (range -82% to 44%), with a proportionality to busulfan metabolism, was found. After 40 years of age, the time effect increased with 4% per year of age (0.6-8%, P = 0.009), causing the effect to increase more than a 2-fold over the observed age-range (0-73 years). Compared to the empirical model, the final semi-mechanistic model increased target attainment from 74% to 76%, mainly through better predictions for adult patients. CONCLUSION: These results suggest that the time-dependent decrease in busulfan clearance may be related to gluthathione depletion. This effect increased with older age (>40 years) and was proportional to busulfan metabolism. The newly constructed semi-mechanistic model could be used to further improve TDM-guided exposure target attainment of busulfan in patients undergoing HCT.

The Predicted Long-Term Benefits of Ensuring Timely Treatment and Medication Adherence in Early Schizophrenia.

The impact of initiatives aimed at reducing time in untreated psychosis during early-stage schizophrenia will be unknown for many years. Thus, we simulate the effect of earlier treatment entry and better antipsychotic drug adherence on schizophrenia-related hospitalizations, receipt of disability benefits, competitive employment, and independent/family living over a ten-year horizon. We predict that earlier treatment entry reduces hospitalizations by 12.6-14.4% and benefit receipt by 7.0-8.5%, while increasing independent/family living by 41.5-46% and employment by 42-58%. We predict larger gains if a pro-adherence intervention is also used. Our findings suggest substantial benefits of timely and consistent early schizophrenia care.

Neither superorganisms nor mere species aggregates: Charles Elton's sociological analogies and his moderate holism about ecological communities.

This paper analyzes community ecologist Charles Elton's ideas on animal communities, and situates them with respect to the classical opposition between organicist-holistic and individualistic-reductionist ecological views drawn by many historians of ecology. It is argued that Elton espoused a moderate ecological holism, which drew a middle way between the stricter ecological holism advocated by organicist ecologists and the merely aggregationist views advocated by some of their opponents. It is also argued that Elton's moderate ecological holism resonated with his preference for analogies between ecological communities and human societies over more common ones between communities and individual organisms. I discuss, on the one hand, how the functionalist-interactionist approach to community ecology introduced by Elton entailed a view of ecological communities as more or less self-maintaining functionally organized wholes, and how his ideas on this matter were incorporated into their views by organicist ecologists Frederic Clements, Victor Shelford, and Warder C. Allee et al. On the other hand, I identify some important divergences between Elton's ecological ideas and those of organicist ecologists. Specifically, I show (1) how Elton's ideas on species distribution, animal migrations, and ecological succession entailed a view of animal communities as exhibiting a weaker degree of part-whole integration than that attributed to them by Clements and Shelford; and (2) how Elton's mixed stance on the balance of nature idea and his associated views on community stability attributed to communities a weaker form of self-regulation than that attributed to them by Allee et al.

What does it cost to redispense unused medications in the pharmacy? A micro-costing study.

BACKGROUND: Redispensing unused medications that have been returned to outpatient pharmacies by patients may reduce waste and healthcare costs. However, little is known regarding the extra costs associated with this process, nor the price level of medications for which this is economically beneficial. The objective of this study was to assess costs associated with redispensing unused medications in the pharmacy and the price level at which redispensing becomes cost-beneficial. METHODS: A micro-costing study was conducted in four Dutch outpatient pharmacies for medications requiring room-temperature storage and requiring refrigeration. First, the pharmacy's necessary additional process steps and resources for redispensing were identified. Second, time required for each process step was simulated. Third, required resources were quantified by calculating labour, purchasing and overhead costs. Lastly, a model with different scenarios was constructed to calculate the price of a medication package at which redispensing becomes cost-beneficial. RESULTS: Three main additional process steps for redispensing were identified: (1) pack medications with product quality indicators before dispensing, (2) assess quality of medications returned to the pharmacy (temperature storage, package integrity, expiry date) and (3a) restock medications fulfilling quality criteria or (3b) dispose of medications not fulfilling criteria. Total time required for all steps up to restock one medication package was on average 5.3 (SD ±0.3) and 6.8 (SD ±0.3) minutes for medications stored at room-temperature and under refrigeration, respectively, and associated costs were €5.54 and €7.61. Similar outcomes were found if a medication package would ultimately be disposed of. The price level primarily depended upon the proportion of dispensed packages returned unused to the pharmacy and fulfilling the quality criteria: if 5% is returned, of which 60% fulfils quality criteria, the price level was €101 per package for medications requiring room-temperature storage and €215 per package for those requiring refrigeration. However, if 10% is returned, of which 60% fulfils the quality criteria, the price level decreases to €53 and €109, respectively (arbitrary proportions). CONCLUSIONS: Redispensing unused medications in the pharmacy is at least cost-beneficial if applied to expensive medications.

[La ménopause et le traitement hormonal de la ménopause : une actualisation]. / Menopause and menopause hormonal treatment : an update.

Postmenopausal hormone therapy (MHT) is mainly used for the relief of menopausal symptoms. It can also be prescribed for the treatment of postmenopausal osteoporosis, but nowadays, other medications are given to older patients for this indication. Current, available data, demonstrates that MHT is beneficial as well as safe for postmenopausal, symptomatic women. Modern regimens of MHT comprise lower dosages of estrogens than in the past, either safer progestins or SERMs. These regimens should be the preferred option for women with a uterus. Non-androgenic progestin may present reduced thrombotic and breast cancer risks, and transdermal oestrogen could have a reduced thrombotic risk. Oestrogen-only therapy is the preferred option for women who underwent a hysterectomy. Vaginal oestrogen therapy is indicated for women with atrophic vaginitis and recurrent urinary tract infections.

Le traitement des symptômes vasomoteurs constitue l'indication principale du traitement hormonal de la ménopause (THM). La seconde indication est le traitement de l'ostéoporose après la ménopause. Toutefois, d'autres produits sont utilisés pour traiter des femmes plus âgées à cette même fin. La balance bénéfice-risque est en faveur du THM pour les femmes postménopausées et symptomatiques, mais les doses d'oestrogène ont été réduites dans les schémas de traitement actualisés. Par ailleurs, ces schémas préconisent l'utilisation soit de progestatifs moins androgéniques et ayant une moindre innocuité que les progestatifs anciens, soit des SERMs. Ces schémas constituent les premiers choix de traitement pour les femmes non-hystérectomisées. Les progestatifs nonandrogéniques sont associés à un risque diminué de thrombose veineuse et de cancer du sein alors que les oestrogènes par voie transdermique présentent un moindre risque de thrombose veineuse. Chez les femmes qui n'ont plus d'utérus, il convient de prescrire des oestrogènes sans progestatifs. Le traitement local par voie vaginale à base d'oestrogènes est indiqué chez les femmes souffrant de vaginite atrophique, entrainant des difficultés sexuelles ou des infections urinaires récidivantes.

Harnessing Scientific and Technological Advances to Improve Equity in Kidney Allocation Policies.

We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αß allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαß allelic (study) versus serologic (current practice) nomenclature. A significant (p < 10-4 ) decrease in cPRA was observed with higher impact for male versus female, and first transplant versus retransplant (p < 10-4 ), affecting mostly patients with moderate cPRA (30-80%). Consequently, the number of patients qualifying for 100% cPRA points according to the United Network for Organ Sharing-Kidney Allocation System decreased by 37%. More critically, by using allelic versus serologic nomenclature for HLA-DQ, the number of PCDs for all patients was increased, with male and first-transplant patients showing a higher expansion compared with female and retransplants. Patients of blood group O showed the highest benefit. The goal of reporting unacceptable antigens is to improve accuracy of virtual crossmatching and increase the likelihood of finding immunologically compatible donors. Our simulation provides strong support for the need to re-evaluate the use of allele typing and how HLA-DQ antigens and antibodies are incorporated into allocation policies to ensure equity.

Health outcomes of bedaquiline in the treatment of multidrug-resistant tuberculosis in selected high burden countries.

BACKGROUND: Less than one-third of patients who are estimated to be infected with multidrug-resistant tuberculosis (MDR-TB) receive MDR-TB treatment regimens, and only 48% of those who received treatment have successful outcomes. Despite current regimens, newer, more effective and cost-effective approaches to treatment are needed. The aim of the study was to project health outcomes and impact on healthcare resources of adding bedaquiline to the treatment regimen of MDR-TB in selected high burden countries: Estonia, Russia, South Africa, Peru, China, the Philippines, and India. METHODS: This study adapted an existing Markov model to estimate the health outcomes and impact on total healthcare costs of adding bedaquiline to current MDR-TB treatment regimens. A price threshold analysis was conducted to determine the price range at which bedaquiline would be cost-effective. RESULTS: Adding bedaquiline to the background regimen (BR) resulted in increased disability-adjusted life years (DALYs) averted, and reduced total healthcare costs (excluding treatment acquisition costs) compared with BR alone in all countries analyzed. Addition of bedaquiline to BR resulted in savings to healthcare costs compared with BR alone in all countries analyzed, with the highest impact expected in Russia (US$194 million) and South Africa (US$43 million). The price per regimen at which bedaquiline would be cost-effective ranged between US$23,904-US$203,492 in Estonia, Russia, Peru, South Africa, and China (high and upper middle-income countries) and between US$6,996-US$20,323 in the Philippines and India (lower middle-income countries); however, these cost-effective prices do not necessarily address concerns about affordability. CONCLUSIONS: Adding bedaquiline to BR provides improvements in health outcomes and reductions in healthcare costs in high MDR-TB burden countries. The range of prices per regimen for which bedaquiline would be cost-effective varied between countries.

Associations Between Personality Traits and Adherence to Antidepressants Assessed Through Self-Report, Electronic Monitoring, and Pharmacy Dispensing Data: A Pilot Study.

Treatment with antidepressants is often compromised by substantial nonadherence. To understand nonadherence, specific medication-related behaviors and beliefs have been studied, but less is known about broader and temporally stable personality "traits." Furthermore, adherence has often been assessed by a single method. Hence, we investigated associations between the Big Five personality traits and adherence assessed by self-report, electronic drug use monitoring, and dispensing data. Using the Big Five Inventory, we assessed the personality traits "openness," "conscientiousness," "extraversion," "agreeableness," and "neuroticism" of patients treated with antidepressants who were invited through community pharmacies. Self-reported adherence was assessed with the Medication Adherence Rating Scale (score >24), electronic monitoring with medication event monitoring system (MEMS) devices (therapy days missed ≤ 10% and < 4 consecutive days missed), and dispensing data (medication possession ratio ≥ 80%). One hundred four women and 33 men participated (mean age, 51; standard deviation, 14). Paroxetine was most frequently prescribed (N = 53, 38%). Logistic regression analysis revealed that of the personality traits, the third and fourth quartiles of "conscientiousness" were associated with better self-reported adherence (odds ratio, 3.63; 95% confidence interval, 1.34-9.86 and odds ratio, 2.97; 95% confidence interval, 1.09-8.08; P ≤ 0.05). No relationships were found between personality traits and adherence assessed through electronic drug use monitoring or dispensing data. We therefore conclude that adherence to antidepressant therapy seems to be largely unrelated to personality traits.

Patient-Reported Factors Associated With Poor Phosphorus Control in a Maintenance Hemodialysis Population.

OBJECTIVE: The purpose of this study was to determine the influence of patient-reported medication adherence and phosphorus-related knowledge on phosphorus control and pharmacy-reported adherence to phosphorus binding medication among patients on maintenance hemodialysis. DESIGN: Retrospective, cross-sectional cohort study. SUBJECTS: Seventy-nine hemodialysis patients (mean age 64.2 years, SD = 14 years; 46.8% female) in a stand-alone hemodialysis unit within an integrated learning healthcare system. Ten percent (10%) of subjects were Caucasian, 42% Latino, 19% African American, and 29% Asian. Forty-eight percent had diabetes; 72% had BMI ≥ 30. Inclusion criteria included the provision of survey data and having medication refill data available in the pharmacy system. 77.2% had mean phosphorus levels ≤ 5.5 mg/dL; 22.8% had mean phosphorus levels > 5.5 mg/dL. INTERVENTION: Subjects were administered the 8-item Morisky Medication Adherence Scale (MMAS-8) and also reported on their phosphorus-related knowledge. MAIN OUTCOME MEASURE: Phosphorus levels within an adequate range. RESULTS: The mean serum phosphorus level was 4.96 mg/dL (SD = 1.21). In the well-controlled group, mean phosphorus was 4.44 mg/dL (SD = 0.76). In the poorly controlled group, mean phosphorus was 6.69 mg/dL (SD = 0.74). A total of 61% of patients reported at least some unintentional medication nonadherence, and 48% reported intentional medication nonadherence. Phosphorus-specific knowledge was low, with just under half of patients reporting that they could not name two high-phosphorus foods or identify a phosphorus-related health risk. Phosphorus binder-related nonadherence was substantially higher in the uncontrolled than the controlled group. Adjusting for age, individuals with poorer self-reported binder adherence were less likely to have controlled phosphorus levels (odds ratio = 0.71, P = .06). CONCLUSION: Phosphorus-related non-adherence, but not low phosphorus-specific knowledge, was associated with poorer phosphorus control. Such findings provide important information for the development of evidence-based strategies for improving phosphorus control among patients on dialysis.

First-Passage Times in d-Dimensional Heterogeneous Media.

Although there are many theoretical studies of the mean first-passage time (MFPT), most neglect the diffusive heterogeneity of real systems. We present exact analytical expressions for the MFPT and residence times of a pointlike particle diffusing in a spherically symmetric d-dimensional heterogeneous system composed of two concentric media with different diffusion coefficients with an absorbing inner boundary (target) and a reflecting outer boundary. By varying the convention, e.g., Ito, Stratonovich, or isothermal, chosen to interpret the overdamped Langevin equation with multiplicative noise describing the diffusion process, we find different predictions and counterintuitive results for the residence time in the outer region and hence for the MFPT, while the residence time in the inner region is independent of the convention. This convention dependence of residence times and the MFPT could provide insights about the heterogeneous diffusion in a cell or in a tumor, or for animal and insect searches inside their home range.