Perceived Sodium Reduction Barriers Among Patients with Chronic Kidney Disease: Which Barriers Are Important and Which Patients Experience Barriers?

Purpose

The purposes of this study were to assess the importance of perceived sodium reduction barriers among patients with chronic kidney disease (CKD) and identify associated sociodemographic, clinical, and psychosocial factors.

Method

A total of 156 patients with CKD completed a questionnaire assessing sodium reduction barriers (18 self-formulated items), depressive symptoms (Beck Depression Inventory), perceived autonomy support (Modified Health Care Climate Questionnaire), and self-efficacy (Partners in Health Questionnaire). Factor analysis was used to identify barrier domains. Correlation coefficients were computed to examine relationships between barrier domains and patient characteristics.

Results

Nine barrier domains were identified. Barriers perceived as important were as follows: high sodium content in products, lack of sodium feedback, lack of goal setting and discussing strategies for sodium reduction, and not experiencing CKD-related symptoms (mean scores > 3.0 on 5-point scales, ranging from 1 ‘no barrier’ to 5 ‘very important barrier’). Other barriers (knowledge, attitude, coping skills when eating out, and professional support) were rated as moderately important (rated around midpoint), and the barrier ‘intrinsic motivation’ was rated as somewhat important (mean score = 1.9). Sodium reduction barrier domains were not associated with gender and kidney function, but were associated with age, level of education, number of comorbidities, perceived autonomy support, depressive symptoms, and self-efficacy (range r = 0.17–0.35). Patients with lower self-efficacy and perceived autonomy support scores experienced most sodium reduction barriers.

Conclusion

Patients with CKD experience multiple important sodium reduction barriers and could benefit from support strategies that target various sodium reduction barriers and strengthen beliefs regarding self-efficacy and autonomy support. Additionally, environmental interventions should be implemented to reduce sodium levels in processed foods.

     

Interleukin-1 May Link Helplessness—Hopelessness with Cancer Progression: A Proposed Model

A model of the relations between psychological factors and cancer progression should include brain and systemic components and their link with critical cellular stages in cancer progression. We present a psychoneuroimmunological (PNI) model that links helplessness- hopelessness (HH) with cancer progression via interleukin-1β (IL-1β . IL-1β was elevated in the brain following exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL-1β. Elevated cerebral IL-1β increased cancer metastasis in animals. Inescapable shock was associated with systemic elevations of IL-1β and peripheral IL-1β was associated with escape from apoptosis, angiogenesis, and metastasis. Involvement of the sympathetic nervous system and the hypothalamic- pituitary- adrenal axis are discussed. Future studies need to identify the role of additional factors in this PNI pathway.     

Telomere loss: mitotic clock or genetic time bomb?

The Holy Grail of gerontologists investigating cellular senescence is the mechanism responsible for the finite proliferative capacity of somatic cells. In 1973, Olovnikov proposed that cells lose a small amount of DNA following each round of replication due to the inability of DNA polymerase to fully replicate chromosome ends (telomeres) and that eventually a critical deletion causes cell death. Recent observations showing that telomeres of human somatic cells act as a mitotic clock, shortening with age both in vitro and in vivo in a replication dependent manne, support this theory's premise. In addition, since telomeres stabilize chromosome ends against recombination, their loss could explain the increased frequency of dicentric chromosomes observed in late passage (senescent) fibroblasts and provide a checkpoint for regulated cell cycle exit. Sperm telomeres are longer than somatic telomeres and are maintained with age, suggesting that germ line cells may express telomerase, the ribonucleoprotein enzyme known to maintain telomere length in immortal unicellar eukaryotes. As predicted, telomerase activity has been found in immortal, transformed human cells and tumour cell lines, but not in normal somatic cells. Telomerase activation may be a late, obligate event in immortalization since many transformed cells and tumour tissues have critically short telomeres. Thus, telomere length and telomerase activity appear to be markers of the replicative history and proliferative potential of cells; the intriguing possibility remains that telomere loss is a genetic time bomb and hence causally involved in cell senescence and immortalization.     

When is Higher Level Cognitive Control Needed for Locomotor Tasks Among Patients with Parkinson’s Disease?

Turning has been implicated as a complex task that requires both motor and cognitive resources. Accumulating evidence shows that patients with Parkinson’s disease (PD) require more steps and more time to complete a turn, however, the role of the prefrontal cortex during turning is not clear. Forty nine patients with PD without freezing of gait (mean age 71.7?±?1.0 years; 67% men, disease duration 9.7?±?1.3 years) performed motor and cognitive tests. Prefrontal activation, specifically in Brodmann area 10 (BA10), during turning and usual walking was measured using functional near infrared spectroscopy (fNIRS). The patients with PD were further divided into two subgroups with high and low functional status based on limitations in community ambulation. General Linear Model analysis adjusted for age, gender, disease duration and turn duration was used to assess differences between tasks and subgroups of patients with PD. In addition, Pearson’s correlation was performed to assess association between BA10 activation and motor and cognitive scores. Activation in BA10 increased during walking (p?<?0.001), while it decreased during turning (p?=?0.006). A comparison between the two subgroups of patients with PD revealed that patients with relatively better ambulation decreased prefrontal activation during turning, as compared to patients with relatively worse ambulation (p?<?0.001). These findings are the first to show that BA10 plays a different role during turning and walking and that ambulation status may alter BA10 activation during turning. Higher prefrontal activation during turning in the subgroup of patients with relatively worse ambulation may reflect a compensatory attempt at improving performance.     

Monitoring Treatment of Patients with Pulmonary Tuberculosis: Can PCR Be Applied?

To assess whether PCR is applicable for monitoring the efficacy of antituberculous treatment, respiratory specimens obtained during treatment and follow-up from sputum smear-positive tuberculosis (TB) patients were examined. First, results of smear, culture, and PCR for Mycobacterium tuberculosis complex (MTB) and an internal inhibition control (MCC) were correlated retrospectively on 1,601 respiratory specimens from patients with no previous cultures of MTB. MTB optical density (OD) values increased to a maximum level of 3.5 to 4.0, with both increasing numbers of acid-fast bacilli and CFU. MTB/MCC OD ratios also increased with both smear and culture grading and correlated significantly better with both than the MTB OD value. Second, changes in MTB OD values and MTB/MCC OD ratios were compared with microscopy and culture for MTB in monthly sputa obtained during treatment and follow-up in 22 smear-positive pulmonary TB patients. Declines in MTB/MCC OD ratios during antituberculous treatment and follow-up were observed. Patients with moderate disease reached the baseline after 6 to 8 months of standard antituberculous treatment regimen, whereas patients with extensive disease were predicted to reach the baseline 1 year or more after the initiation of treatment. Although PCR detects both dead and live bacteria, we believe that PCR can be used to assess the efficacy of antituberculous treatment since increases or slow reductions in MTB/MCC OD ratios would indicate nonoptimal treatment, noncompliance, reduced bioavailability of drugs, or resistant strains of MTB and thereby would identify patients at risk for treatment failure or reactivation.     

Transplant Decisions in Patients with Myelofibrosis: Should Mutations Be the Judge?

The prognosis of myeloproliferative neoplasms, including primary myelofibrosis (PMF), polycythemia vera, and essential thrombocythemia varies considerably, between these disorders as well as within each diagnosis. Molecular studies have identified “driver mutations” in JAK2, MPL1, and CALR and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2, and SRSF2, that affect prognosis differentially. Patients with mutations in CALR (type1) have a better outlook than patients with mutations in JAK2 or MPL, whereas patients without any of the driver mutations (triple negative) have the shortest life expectancy. Mutations in ASXL1, EZH2, and SRSF2 may be associated with shortened survival, and IDH mutations carry a higher risk of leukemic transformation. The combination and number of mutations are more important than a given single mutation. Mutations also appear to impact the outcome of hematopoietic cell transplantation (HCT), currently the only treatment with curative potential. Based on available data, the best post-HCT outcome is observed with CALR mutations. Triple negativity has a negative impact. The data on JAK2 are controversial. Mutations in ASXL1 or IDH1/2 reduce the probability of progression-free survival after HCT, although the impact of ASXL1 differs between patients with primary and secondary myelofibrosis. Although it is not clear to what extent HCT can overcome the risks associated with a given mutational pattern, at present, early HCT should be considered in triple-negative patients and patients with PMF who harbor mutations in ASXL1. Mutations in EZH2, SRSF2, or IDH, particularly if combined with other mutations, should also lead to consideration of HCT. Further studies are needed to validate the present observations and determine the impact of additional mutations that have been identified.     

Busulfan Pharmacokinetics and Precision Dosing: Are Patients with Fanconi Anemia Different?

It is well known that pharmacokinetics (PK)-guided busulfan (BU) dosing increases engraftment rates and lowers hepatotoxicity in patients undergoing hematopoietic cell transplantation (HCT). However, there are no published PK data in patients with Fanconi anemia (FA), who are known to have baseline DNA repair defect and related inherent sensitivity to chemotherapy. In our prospective, multi-institutional study of alternative donor HCT for FA using chemotherapy-only conditioning, we replaced the single dose of total-body irradiation with BU at initial doses of 0.8 to 1.0 mg/kg and 0.6 to 0.8 mg/kg given i.v. every 12 hours for 4 doses. Patients received the first dose of i.v. busulfan on day –8, and blood levels for PK were obtained. PK samples were drawn following completion of infusion. BU PK levels were collected at 2 hours, 2 hours and 15 minutes, and 4, 5, 6, and 8 hours from the start of infusion. The remaining 3 doses of BU were given on days –7 and –6. Thirty-seven patients with available BU PK data with a median age of 9.2 years (range, 4.3 to 44 years) are included in the final analyses. The overall BU PK profile in patients with FA is similar to non-FA patients after considering their body weight. In our cohort, a strong correlation between BU clearance and weight supports current practice of per kilogram dosing. However, not surprisingly, we show that the disease (ie, host) sensitivity related to FA is the main determinant of total dose of BU that can be safely administered to patients in this high-risk population. On the basis of our results, we propose an optimal BU concentration at steady-state level of ≤350 ng/mL (equivalent to total cumulative exposure of 16.4 mg*h/L for 4 doses over 2 days) for patients with FA undergoing HCT. To our knowledge, this is the first and largest report of prospective BU PK in patients with FA undergoing HCT, providing an optimal BU target cutoff to achieve stable donor engraftment while avoiding excessive toxicity.     

Telomere length and cardiovascular aging: the means to the ends?

Epidemiologic and other evidence clearly indicates that peripheral blood leukocyte telomere length, a systemic marker for biological aging, can be useful as a cardiovascular aging biomarker. Although telomere biology might yield new insights into the underlying molecular biology of vascular aging and even radically improve current cardiovascular risk stratification, the specific nature of the association between telomere length and cardiovascular disease still remains to be elucidated. Here, we review several candidate hypotheses and critically review supporting and contesting scientific evidence for the underlying theories. For each hypothesis, we discuss the potential implications. We conclude that the most promising theory is based on an acceleration of the telomere attrition rate due to cardiovascular aging related factors, possibly complemented by telomere mediated hematopoietic senescence.     

Narcolepsy with Long Sleep Time: A Specific Entity?

Background:

The classical narcolepsy patient reports intense feelings of sleepiness (with/out cataplexy), normal or disrupted nighttime sleep, and takes short and restorative naps. However, with long-term monitoring, we identified some narcoleptics resembling patients with idiopathic hypersomnia.

Objective:

To isolate and describe a new subtype of narcolepsy with long sleep time).

Setting:

University Hospital

Design:

Controlled, prospective cohort

Participants:

Out of 160 narcoleptics newly diagnosed within the past 3 years, 29 (18%) had a long sleep time (more than 11 h/24 h). We compared narcoleptics with (n = 23) and without (n = 29) long sleep time to 25 hypersomniacs with long sleep time and 20 healthy subjects.

Intervention:

Patients and controls underwent face-to face interviews, questionnaires, human leukocyte antigen (HLA) genotype, an overnight polysomnography, multiple sleep latency tests, and 24-h ad libitum sleep monitoring.

Results:

Narcoleptics with long sleep time had a similar disease course and similar frequencies of cataplexy, sleep paralysis, hallucinations, multiple sleep onset in REM periods, short mean sleep latencies, and HLA DQB1*0602 positivity as narcoleptics with normal sleep time did. However, they had longer sleep time during 24 h, and higher sleep efficiency, lower Epworth Sleepiness Scale scores, and reported their naps were more often unrefreshing. Only 3/23 had core narcolepsy (HLA and cataplexy positive).

Conclusions:

The subgroup of narcoleptics with a long sleep time comprises 18% of narcoleptics. Their symptoms combine the disabilities of both narcolepsy (severe sleepiness) and idiopathic hypersomnia (long sleep time and unrefreshing naps). Thus, they may constitute a group with multiple arousal system dysfunctions.

Citation:

Vernet C; Arnulf I. Narcolepsy with long sleep time: a specific entity? SLEEP 2009;32(9):1229-1235.     

Coping with urbanization: A cardiometabolic risk?: The THUSA study

An assessment of specific coping styles in rural–urban Africans is done to evaluate its contribution as cardiometabolic risk factor. In total, 608 apparently healthy Africans were included in a cross-sectional comparative study from the North-West Province in South Africa. The adapted and translated COPE Questionnaire classified participants according to their responses into active (AC) or passive (PC) copers. Fasting resting metabolic syndrome (MS) indicators using the WHO definition (glucose, high density lipoproteins, waist/hip ratio, hypertension prevalence, and triglyceride) and associated MS values, i.e. fibrinogen were obtained. The Finapres recorded resting blood pressure continuously. Co-variates for all statistical analyses included age, body mass index (BMI) and lifestyle factors (alcohol consumption, smoking habits and physical activity). The only MS values prevalent in urbanized participants were higher hypertension prevalence rates and fibrinogen (women only) compared to their rural counterparts. Adding coping styles, it was mainly the urbanized AC participants that indicated higher MS values (hypertension prevalence, glucose and fibrinogen) when compared to their rural and PC counterparts. In conclusion, urbanization is associated with enhanced blood pressure and fibrinogen (women) values only. Coping as cardiometabolic risk is accentuated in the urbanized AC group, especially the men. The urbanized AC group with their higher blood pressure values and more MS indicators appears to have behaviorally an AC style but physiologically a dissociated AC style.     

Carboxypeptidase D: A Novel TGF-β Target Gene Dysregulated in Patients with Lupus Erythematosus

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that mainly acts as an inhibitor of immune functions. A lack of functional TGF-β leads to autoimmune disease in animal models and dysregulated TGF-β signaling is implicated in human autoimmune diseases. To define target genes that play a part in the inhibitory role of TGF-β in the immune system, we have identified genes stimulated by TGF-β in macrophages by gene-chip analysis. One of the TGF-β regulated genes is carboxypeptidase D (CpD), a 180-kDa type I membrane protein. We have demonstrated that CpD is regulated by TGF-β in various cell types of both, murine and human origin and, interestingly, is significantly downregulated in CD14 positive cells isolated from patients with lupus erythematosus (LE). Moreover, we show that downregulation of CpD leads to downmodulation of TGF-β itself, suggesting a role for CpD in a positive feedback loop, providing further evidence for a role of this enzyme in LE. To our knowledge, this is the first report that demonstrates carboxypeptidase D as a TGF-β target gene that is implicated in the pathogenesis of LE.     

Success in Weight Management Among Patients with Type 2 Diabetes: Do Perceived Autonomy Support,Autonomous Motivation,and Self-Care Competence Play a Role?

Based on self-determination theory (SDT), this study investigated whether the three central SDT variables—perceived autonomy support (from a physician), autonomous motivation and self-care competence—were associated with success in weight management (SWM) among primary care patients with type 2 diabetes when the effect of other important life-context factors was controlled for. Patients participated in a mail survey in 2011. Those who had tried to change their health behavior during the past two years in order to lose weight, either with or without success (n = 1433, mean age 63 years, 50% men), were included in this study. The successors were more autonomously motivated and energetic than the non-successors. Moreover, male gender, younger age, taking oral medication only, and receiving less social support in diabetes care predicted better success. Autonomous motivation predicted SWM; self-care competence also played a role by partly mediating the effect of autonomous motivation on SWM. These results support the idea of SDT that internalizing the value of weight management and its health benefits is necessary for long-term maintenance of health behavior change. Perceived autonomy support was not directly associated with SWM. However, physicians can promote patients' weight management by supporting their autonomous motivation and self-care competence.