Symptom burden in chronic kidney disease : a review of recent literature

Background: People living with chronic kidney disease (CKD) experience multiple symptoms due to both the disease and its treatment, these symptoms are often under recognized. The majority of studies have focused on an individual symptom; however these symptoms rarely occur in isolation and may instead occur in clusters. Aim of review: This review investigated the total symptom burden in advanced CKD (stages 4 and 5) and identified the key instruments that are used to assess multiple symptoms. Methods: A literature search from 2006 to 2012 was undertaken and a total of 19 articles were included. Result: The most common CKD symptoms were fatigue or lack of energy, feeling drowsy, pain and pruritus. However, symptom assessment instruments varied between studies, often with inconsistent or inadequate symptom dimensions. Conclusion: People with CKD experience a high burden of symptom, although little is known about the burden for people with CKD stage 4 and for those with CKD stage 5 receiving PD. This review recommends that a full range of symptoms be assessed for those at different stages of CKD. Improved understanding of the burden of symptoms could be used as the basis for treatment choices and for identifying priorities which are likely to contribute to a better quality of life and improve the quality of care.

Effect of chronic exercise on appetite control in overweight and obese individuals

Purpose: The effect of exercise on body mass is likely to be partially mediated through changes in appetite control. However, no studies have examined the effect of chronic exercise on obestatin and cholecystokinin (CCK) plasma concentrations or the sensitivity to detect differences in preload energy in obese individuals. The objective of this study was to investigate the effects of chronic exercise on 1) fasting and postprandial plasma concentrations of obestatin, CCK, leptin, and glucose insulinotropic peptide (GIP) and 2) the accuracy of energy compensation in response to covert preload manipulation. Methods: This study used a 12-wk supervised exercise program in 22 sedentary overweight/obese individuals. Fasting/postprandial plasma concentrations of obestatin, CCK, leptin, and GIP were assessed before and after the intervention. Energy compensation at a 30-min test meal after a high-energy (607 kcal) or a low-energy (246 kcal) preload and for the rest of the day (cumulative energy intake [EI]) was also measured. Results: There was a significant reduction in the plasma concentration of fasting plasma GIP and both fasting and postprandial leptin concentrations after the exercise intervention (P < 0.05 for all). No significant changes were observed for CCK or obestatin. A significant preload–exercise interaction (P = 0.011) was observed on cumulative EI and energy compensation for the same period (−87% ± 196% vs 68% ± 165%, P = 0.011). Weight loss (3.5 ± 1.4 kg, P < 0.0001) was not correlated with changes in energy compensation. Conclusions: This study suggests that exercise improves the accuracy of compensation for previous EI, independent of weight loss. Unexpectedly, and in contrast to GIP and leptin, exercise-induced weight loss had no effect on obestatin or CCK concentrations.

The hyperthermic patient

Concepts used in this chapter include: Thermoregulation:- Thermoregulation refers to the body’s sophisticated, multi-system regulation of core body temperature. This hierarchical system extends from highly thermo-sensitive neurons in the preoptic region of the brain proximate to the rostral hypothalamus, down to the brain stem and spinal cord. Coupled with receptors in the skin and spine, both central and peripheral information on body temperature is integrated to inform and activate the homeostatic mechanisms which maintain our core temperature at 37oC1. Hyperthermia:- An imbalance between the metabolic and external heat accumulated in the body and the loss of heat from the body2. Exertional heat stroke:- A disorder of excessive heat production coupled with insufficient heat dissipation which occurs in un-acclimated individuals who are engaging in over-exertion in hot and humid conditions. This phenomenon includes central nervous system dysfunction and critical dysfunction to all organ systems including renal, cardiovascular, musculoskeletal and hepatic functions. Non-exertional heat stroke:- In contrast to exertional heatstroke as a consequence of high heat production during strenuous exercise, non-exertional heatstroke results from prolonged exposure to high ambient temperature. The elderly, those with chronic health conditions and children are particularly susceptible.3 Rhabdomylosis:- An acute, sometimes fatal disease characterised by destruction of skeletal muscle. In exertional heat stroke, rhabdomylosis occurs in the context of strenuous exercise when mechanical and/or metabolic stress damages the skeletal muscle, causing elevated serum creatine kinease. Associated with this is the potential development of hyperkalemia, myoglobinuria and renal failure. Malignant hyperthermia:- Malignant hyperthermia is “an inherited subclinical myopathy characterised by a hypermetabolic reaction during anaesthesia. The reaction is related to skeletal muscle calcium dysregulation triggered by volatile inhaled anaesthetics and/or succinylcholine.”4 Presentation includes skeletal muscle rigidity, mixed metabolic and respiratory acidosis, tachycardia, hyperpyrexia, rhabdomylosis, hyperkalaemia, elevated serum creatine kinease, multi-organ failure, disseminated intravascular coagulation and death.5

Neighbourhood disadvantage, individual-level socioeconomic position, and self-reported chronic arthritis : a cross-sectional multilevel study

Objective: To examine the association between individual- and neighborhood-level disadvantage and self-reported arthritis. Methods: We used data from a population-based cross-sectional study conducted in 2007 among 10,757 men and women ages 40–65 years, selected from 200 neighborhoods in Brisbane, Queensland, Australia using a stratified 2-stage cluster design. Data were collected using a mail survey (68.5% response). Neighborhood disadvantage was measured using a census-based composite index, and individual disadvantage was measured using self-reported education, household income, and occupation. Arthritis was indicated by self-report. Data were analyzed using multilevel modeling. Results: The overall rate of self-reported arthritis was 23% (95% confidence interval [95% CI] 22–24). After adjustment for sociodemographic factors, arthritis prevalence was greatest for women (odds ratio [OR] 1.5, 95% CI 1.4–1.7) and in those ages 60–65 years (OR 4.4, 95% CI 3.7–5.2), those with a diploma/associate diploma (OR 1.3, 95% CI 1.1–1.6), those who were permanently unable to work (OR 4.0, 95% CI 3.1–5.3), and those with a household income <$25,999 (OR 2.1, 95% CI 1.7–2.6). Independent of individual-level factors, residents of the most disadvantaged neighborhoods were 42% (OR 1.4, 95% CI 1.2–1.7) more likely than those in the least disadvantaged neighborhoods to self-report arthritis. Cross-level interactions between neighborhood disadvantage and education, occupation, and household income were not significant. Conclusion: Arthritis prevalence is greater in more socially disadvantaged neighborhoods. These are the first multilevel data to examine the relationship between individual- and neighborhood-level disadvantage upon arthritis and have important implications for policy, health promotion, and other intervention strategies designed to reduce the rates of arthritis, indicating that intervention efforts may need to focus on both people and places.

Nutritional support and functional capacity in chronic obstructive pulmonary disease: A systematic review and meta-analysis

Currently there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCTs (n = 448) in stable COPD patients investigating the effects of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 10 RCTs), enteral tube feeding (1 RCT)] versus control on functional outcomes. Meta-analysis of the changes induced by intervention found that whilst respiratory function (FEV(1,) lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (PI max +3.86 SE 1.89 cm H(2) O, P = 0.041; PE max +11.85 SE 5.54 cm H(2) O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved, and associated with weight gains of ≥ 2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta-analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta-analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.

Tenofovir-associated proteinuria

Proteinuria was observed in 27% of 153 patients taking tenofovir for more than 1 year. Concomitant protease inhibitor therapy and cumulative tenofovir exposure were independently associated with proteinuria in this cohort. Proteinuria was reversible in 11 of 12 patients who ceased tenofovir because of proteinuria without altering other medications. Clinicians should be aware that tenofovir can cause reversible proteinuria in patients with HIV.

Quality of life in chronic fatigue syndrome

Whilst the debilitating fatigue experienced in patients suffering from Chronic Fatigue Syndrome (CFS) results in a subjective marked impairment in functioning, little research has investigated the impact of this disorder on quality of life. Forty-seven subjects with a confirmed diagnosis of CFS and 30 healthy controls were compared using the Sickness Impact Profile (SIP). A subgroup of subjects were interviewed regarding the impact CFS has had on their social and family relationships, work and recreational activities. Results from both the SIP and the interview revealed that CFS subjects had significantly impaired quality of life, especially in areas of social functioning. These findings highlight the importance of addressing the social isolation and loss of role functioning experienced by CFS sufferers.

Utility of an alternative bicycle commute route of lower proximity to motorised traffic in decreasing exposure to ultra-fine particles, respiratory symptoms and airway inflammation - a structured exposure experiment

Background: Bicycle commuting in an urban environment of high air pollution is known as a potential health risk, especially for susceptible individuals. While risk management strategies aimed to reduce motorised traffic emissions exposure have been suggested, limited studies have assessed the utility of such strategies in real-world circumstances. Objectives: The potential of reducing exposure to ultrafine particles (UFP; < 0.1 µm) during bicycle commuting by lowering interaction with motorised traffic was investigated with real-time air pollution and acute inflammatory measurements in healthy individuals using their typical, and an alternative to their typical, bicycle commute route. Methods: Thirty-five healthy adults (mean ± SD: age = 39 ± 11 yr; 29% female) each completed two return trips of their typical route (HIGH) and a pre-determined altered route of lower interaction with motorised traffic (LOW; determined by the proportion of on-road cycle paths). Particle number concentration (PNC) and diameter (PD) were monitored in real-time in-commute. Acute inflammatory indices of respiratory symptom incidence, lung function and spontaneous sputum (for inflammatory cell analyses) were collected immediately pre-commute, and one and three hours post-commute. Results: LOW resulted in a significant reduction in mean PNC (1.91 x e4 ± 0.93 x e4 ppcc vs. 2.95 x e4 ± 1.50 x e4 ppcc; p ≤ 0.001). Besides incidence of in-commute offensive odour detection (42 vs. 56 %; p = 0.019), incidence of dust and soot observation (33 vs. 47 %; p = 0.038) and nasopharyngeal irritation (31 vs. 41 %; p = 0.007), acute inflammatory indices were not significantly associated to in-commute PNC, nor were these indices reduced with LOW compared to HIGH. Conclusions: Exposure to PNC, and the incidence of offensive odour and nasopharyngeal irritation, can be significantly reduced when utilising a strategy of lowering interaction with motorised traffic whilst bicycle commuting, which may bring important benefits for both healthy and susceptible individuals.

Malaria antibody persistence correlates with duration of exposure

Background and Objectives  In Australia, the risk of transfusion-transmitted malaria is managed through the identification of ‘at-risk’ donors, antibody screening enzyme-linked immunoassay (EIA) and, if reactive, exclusion from fresh blood component manufacture. Donor management depends on the duration of exposure in malarious regions (>6 months: ‘Resident’, <6 months: ‘Visitor’) or a history of malaria diagnosis. We analysed antibody testing and demographic data to investigate antibody persistence dynamics. To assess the yield from retesting 3 years after an initial EIA reactive result, we estimated the proportion of donors who would become non-reactive over this period. Materials and Methods  Test results and demographic data from donors who were malaria EIA reactive were analysed. Time since possible exposure was estimated and antibody survival modelled. Results  Among seroreverters, the time since last possible exposure was significantly shorter in ‘Visitors’ than in ‘Residents’. The antibody survival modelling predicted 20% of previously EIA reactive ‘Visitors’, but only 2% of ‘Residents’ would become non-reactive within 3 years of their first reactive EIA. Conclusion  Antibody persistence in donors correlates with exposure category, with semi-immune ‘Residents’ maintaining detectable antibodies significantly longer than non-immune ‘Visitors’.

Spatial variation of particle number concentration in school microscale environments and its impact on exposure assessment

It has not yet been established whether the spatial variation of particle number concentration (PNC) within a microscale environment can have an effect on exposure estimation results. In general, the degree of spatial variation within microscale environments remains unclear, since previous studies have only focused on spatial variation within macroscale environments. The aims of this study were to determine the spatial variation of PNC within microscale school environments, in order to assess the importance of the number of monitoring sites on exposure estimation. Furthermore, this paper aims to identify which parameters have the largest influence on spatial variation, as well as the relationship between those parameters and spatial variation. Air quality measurements were conducted for two consecutive weeks at each of the 25 schools across Brisbane, Australia. PNC was measured at three sites within the grounds of each school, along with the measurement of meteorological and several other air quality parameters. Traffic density was recorded for the busiest road adjacent to the school. Spatial variation at each school was quantified using coefficient of variation (CV). The portion of CV associated with instrument uncertainty was found to be 0.3 and therefore, CV was corrected so that only non-instrument uncertainty was analysed in the data. The median corrected CV (CVc) ranged from 0 to 0.35 across the schools, with 12 schools found to exhibit spatial variation. The study determined the number of required monitoring sites at schools with spatial variability and tested the deviation in exposure estimation arising from using only a single site. Nine schools required two measurement sites and three schools required three sites. Overall, the deviation in exposure estimation from using only one monitoring site was as much as one order of magnitude. The study also tested the association of spatial variation with wind speed/direction and traffic density, using partial correlation coefficients to identify sources of variation and non-parametric function estimation to quantify the level of variability. Traffic density and road to school wind direction were found to have a positive effect on CVc, and therefore, also on spatial variation. Wind speed was found to have a decreasing effect on spatial variation when it exceeded a threshold of 1.5 (m/s), while it had no effect below this threshold. Traffic density had a positive effect on spatial variation and its effect increased until it reached a density of 70 vehicles per five minutes, at which point its effect plateaued and did not increase further as a result of increasing traffic density.

Indoor aerosols : from personal exposure to risk assessment

Motivated by growing considerations of the scale, severity and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19-76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden-of-disease from particulate matter exposure was due to indoor generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.

Individual, environmental, and meteorological predictors of daily personal ultraviolet radiation exposure measurements in a United States cohort study

Background Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements. Methods We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables. Results The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R2 = 0.25). Conclusions In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.

Histopathological examination of chronic laminitis in Kaimanawa feral horses of New Zealand

AIMS: To investigate the prevalence, histopathological and histomorphometric presentation of chronic laminitis in a population of Kaimanawa feral horses. METHODS: Following the capture and euthanasia of feral horses from the Kaimanawa Ranges of New Zealand, the left forefoot of 28 stallions and 28 mares aged between 6 and 12 years were removed and processed for histology. Sections of lamellar samples from each horse were examined using light microscopy. The presence of laminitis was assessed and the histopathological lesions were described. Horses were grouped by histological diagnosis into laminitic and non-laminitic groups and histomorphometric analysis was conducted and compared between groups. The parameters examined were total length of primary epidermal lamellae (PEL), keratinised length of PEL, and the length of secondary epidermal lamellae (SEL) at the abaxial end and axial end of each PEL. RESULTS: Of the horses examined, 25 (45%) were diagnosed with chronic laminitis. The most prevalent histopathological features were the presence of excessive cap horn, and multi-branched and attenuated SEL. Histomorphometric assessment of the lamellar architecture revealed no difference in morphometric measurements between the normal and laminitic groups for any parameter measured (p>0.05). CONCLUSIONS: The current study found a high prevalence of laminitis in feral Kaimanawa horses. The reason for this in the Kaimanawa population is not known. Histomorphometric analysis may not be a good indicator of chronic laminitis in feral horses. CLINICAL RELEVANCE: It is an important finding that the feral horse lifestyle in the environment of the Kaimanawa Ranges in New Zealand offers no protection against foot disease. The finding suggests that horses are vulnerable to laminitis whether in domestic care or in a feral habitat.

Mid-gestation intra-amniotic infection with Ureaplasma parvum is resolved within spiny mice (Acomys cahirinus) by term delivery: but caused chronic infection of fetal lungs and placentae

Background: Ureaplasma species in amniotic fluid at the time of second-trimester amniocentesis increases the risk of preterm birth, but most affected pregnancies continue to term (Gerber et al. J Infect Dis 2003). We aimed to model intra-amniotic (IA) ureaplasma infection in spiny mice, a species with a relatively long gestation (39 days) that allows investigation of the disposition and possible clearance of ureaplasmas in the feto-placental compartment. Method: Pregnant spiny mice received IA injections of U. parvum serovar 6 (10µL, 1x104 colony-forming-units in PBS) or 10B media (10µL; control) at 20 days (d) of gestation (term=39d). At 37d fetuses (n=3 ureaplasma, n=4 control) were surgically delivered and tissues were collected for; bacterial culture, ureaplasma mba and urease gene expression by PCR, tissue WBC counts and indirect fluorescent antibody (IFA) staining using anti-ureaplasma serovar 6 (rabbit) antiserum. Maternal and fetal plasma IgG was measured by Western blot. Results: Ureaplasmas were not detected by culture or PCR in fetal or maternal tissues but were visualized by IFA within placental and fetal lung tissues, in association with inflammatory changes and elevated WBC counts (p<0.0001). Anti-ureaplasma IgG was detected in maternal (2/2 tested) and fetal (1/2 tested) plasma but not in controls (0/3). Conclusions: IA injection of ureaplasmas in mid-gestation spiny mice caused persistent fetal lung and placental infection even though ureaplasmas were undetectable using standard culture or PCR techniques. This is consistent with resolution of IA infection, which may occur in human pregnancies that continue to term despite detection of ureaplasmas in mid-gestation.