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Background: There is limited research quantifying the direct and indirect economic costs associated with intellectual disability (ID) in Australia. Costs incurred by families, governments and broader society include time spent providing care, absenteeism and increased healthcare utilisation. The purpose of this research is to quantify the costs associated with ID in childhood using a range of methods to collect cost data. Methods: Costs included healthcare service utilisation, pharmaceutical use, caregiver productivity losses and time spent providing care because of the child's disability. The sample comprised caregivers with a child with ID aged between 2 and 10 years old recruited in Australia. Healthcare service utilisation and pharmaceutical use were obtained from routinely collected administrative claims data. Healthcare utilisation not captured in the routinely collected administrative data and absenteeism data were obtained from a retrospective recall‐based questionnaire. Time spent providing care because of the child's disability was obtained using a time‐use diary. Results: The total cost of ID in Australia was estimated to be AUD 72 027 per year per child, and the total cost of ID in childhood was estimated to be AUD 12.5 billion per year. The cost to governments of ID in childhood was estimated to be AUD 6385 per child per year, resulting in a total cost to government of AUD 1.1 billion per year. Conclusions: This is the first study to estimate the direct and indirect costs associated with ID in childhood. The results of this research demonstrate the considerable economic impact of ID in childhood on families, governments and broader society in terms of both direct and indirect costs. An understanding of the cost implications of any intervention are critical in assisting policymakers in planning and prioritising of health services. [ABSTRACT FROM AUTHOR]

Background: Children with intellectual disability (ID) frequently have significant educational, social and health care needs, resulting in caregivers often experiencing a wide range of negative effects. This paper aims to determine the impact of childhood ID on caregivers' health‐related quality of life (HRQoL) across co‐morbid diagnostic groups. The second aim of this study is to determine the risk factors associated with lower HRQoL in this population. Methods: Caregivers of a child with ID aged between 2 and 12 years old completed an online survey to determine their HRQoL using the EQ‐5D‐5L measure. They were also asked demographic questions and about their dependent child's level of behavioural and emotional difficulties. Results: Of the total sample of 634 caregivers, 604 caregivers completed all five questions of the EQ‐5D‐5L. The mean age of caregivers was 39.1 years and 91% were women. Caregivers spent on average 66.6 h per week caring for their child related to their child's disability. The mean EQ‐5D‐5L score of caregivers was 0.80 (95% confidence interval: 0.79, 0.82), which is below the estimated Australian population norms (mean utility score of 0.92) for the age‐equivalent population. Caregivers of children with autism spectrum disorders reported the lowest HRQoL (0.77, 95% confidence interval: 0.74, 0.79) of the five included co‐morbid diagnostic groups. Caregivers with a lower income, a perceived low level of social support and children with higher degree of behavioural and emotional problems were likely to have a statistically lower HRQoL. Conclusions: This is the first study to produce utility values for caregivers of children with ID. The utility values can be used to compare health states and can be used to inform comparative cost‐effectiveness analyses. Demonstrating that caregivers of children with ID have reduced HRQoL and that this is associated with the degree of behavioural and emotional problems has important policy implications, highlighting the potential for policy interventions that target behavioural and emotional problems to improve outcomes for caregivers. [ABSTRACT FROM AUTHOR]

Two guidelines about opioid use in chronic pain management were published in 2017: the Canadian Guideline for Opioids for Chronic Non-Cancer Pain and the European Pain Federation position paper on appropriate opioid use in chronic pain management. Though the target populations for the guidelines are the same, their recommendations differ depending on their purpose. The intent of the Canadian guideline is to reduce the incidence of serious adverse effects. Its goal was therefore to set limits on the use of opioids. In contrast, the European Pain Federation position paper is meant to promote safe and appropriate opioid use for chronic pain. The content of the two guidelines could have unintentional consequences on other populations that receive opioid therapy for symptom management, such as patients with cancer. In this article, we present expert opinion about those chronic pain management guidelines and their impact on patients with cancer diagnoses, especially those with histories of substance use disorder and psychiatric conditions. Though some principles of chronic pain management can be extrapolated, we recommend that guidelines for cancer pain management should be developed using empirical data primarily from patients with cancer who are receiving opioid therapy. [ABSTRACT FROM AUTHOR]

Introduction An initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise; however, the neuromuscular adaptations owing to this phenomenon are unknown. Aim To determine whether neuromuscular disturbances are modulated following a repeated bout of eccentric exercise. Methods Following eccentric exercise performed with the elbow flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase (CK) and voluntary activation (VA) using motor point and motor cortex stimulation at baseline, immediately post-exercise and at 1, 2, 3, 4 and 7 days post-exercise on two occasions, separated by 3 weeks. Results Significant muscle damage and fatigue were evident following the first exercise bout; maximal voluntary contraction ( MVC) was reduced immediately by 35% and remained depressed at 7 days post-exercise. Soreness and CK release peaked at 3 and 4 days post-exercise respectively. Resting twitch force remained significantly reduced at 7 days (−48%), whilst VA measured with motor point and motor cortex stimulation was reduced until 2 and 3 days respectively. A repeated bout effect ( RBE) was observed with attenuated soreness and CK release and a quicker recovery of MVC and resting twitch force. A similar decrement in VA was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of, VA measured using motor cortical stimulation. Conclusion Our data suggest that the RBE may be explained, partly, by a modification in motor corticospinal drive. [ABSTRACT FROM AUTHOR]

The development of central fatigue is prominent following exercise-induced hyperthermia, but the contribution of supraspinal fatigue is not well understood. Seven endurance-trained cyclists (mean ± SD peak O2 uptake, 62.0 ± 5.6 mL/kg/min) completed two high-intensity constant-load cycling trials (296 ± 34 W) to the limit of tolerance in a hot (34 °C, 20% relative humidity) and, on a separate occasion, for the same duration, a control condition (18 °C, 20% relative humidity). Core body temperature ( Tc) was measured throughout. Before and immediately after each trial, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation were obtained from the knee extensors to assess neuromuscular and corticospinal function, respectively. Exercise time was 11.4 ± 2.6 min. Peak Tc was higher in the hot compared with control (38.36 ± 0.43 °C vs 37.86 ± 0.36 °C; P = 0.035). Post-exercise reductions in maximal voluntary contraction force (13 ± 9% vs 9 ± 5%), potentiated twitch force (16 ± 12% vs 21 ± 13%) and voluntary activation (9 ± 7% vs 7 ± 7%) were similar in hot and control trials, respectively. However, cortical voluntary activation declined more in the hot compared with the control (8 ± 3% vs 3 ± 2%; P = 0.001). Exercise-induced hyperthermia elicits significant central fatigue of which a large portion can be attributed to supraspinal fatigue. These data indicate that performance decrements in the heat might initially originate in the brain. [ABSTRACT FROM AUTHOR]

Aims We asked whether acclimatization to chronic hypoxia ( CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia ( AH). Methods Seven recreationally active participants performed identical bouts of constant-load cycling (131 ± 39 W, 10.1 ± 1.4 min) on three occasions: (i) in normoxia (N, PIO2, 147.1 mmHg); (ii) in AH ( FIO2, 0.105; PIO2, 73.8 mmHg); and (iii) after 14 days in CH (5260 m; PIO2, 75.7 mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared-spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch responses to femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and corticospinal function. Results In AH, prefrontal oxygenation declined at rest (Δ7 ± 5%) and end-exercise (Δ26 ± 13%) ( P < 0.01); the degree of deoxygenation in AH was greater than N and CH ( P < 0.05). The cerebral O2 delivery index (MCAV × CaO2) was 19 ± 14% lower during the final minute of exercise in AH compared to N ( P = 0.013) and 20 ± 12% lower compared to CH ( P = 0.040). Maximum voluntary and potentiated twitch force were decreased below baseline after exercise in AH and CH, but not N. Cortical voluntary activation decreased below baseline after exercise in AH (Δ11%, P = 0.014), but not CH (Δ6%, P = 0.174) or N (Δ4%, P = 0.298). A twofold greater increase in motor-evoked potential amplitude was evident after exercise in CH compared to AH and N. Conclusion These data indicate that exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days of acclimatization to altitude. The reduced development of supraspinal fatigue in CH may have been attributable to increased corticospinal excitability, consequent to an increased cerebral O2 delivery. [ABSTRACT FROM AUTHOR]

Abstract: Little is known regarding the modulation and the plasticity of the neural pathway interconnecting elements of the central nervous system and skeletal muscle in resistant-trained individuals. The aim of the study was to compare corticospinal and spinal responses measured during dynamic muscle contractions of the tibialis anterior in resistance trained (RT) and un-trained (UT) males. Nine UT and 10 RT male volunteers reported to the laboratory 24h following a familiarisation session. Motor evoked potentials (MEPs) and the cortical silent period were evoked using transcranial magnetic stimulation at a range of contraction intensities and was delivered as the ankle passed 90° during shortening and lengthening contractions. The Hoffmann reflex (H-reflex) and V-waves were evoked with peripheral nerve stimulation. Despite the RT group being significantly stronger during shortening (28%; P =0.023: CI=1.27–15.1Nm), lengthening (25%; P =0.041: CI=0.27–17.0Nm) and isometric muscle actions (20%; P =0.041; CI=0.77–14.9Nm), no differences between the groups existed for corticospinal or spinal variables. Lack of detectable differences between RT and UT individuals may be linked to minimal exposure to task specific, isolated high intensity resistance training of the TA muscle. [Copyright &y& Elsevier]

The aim of this study was to determine the applicability and reliability of a transcranial magnetic stimulation twitch interpolation technique for measuring voluntary activation of a lower limb muscle group. Cortical voluntary activation of the knee extensors was determined in nine healthy men on two separate visits by measuring superimposed twitch torques evoked by transcranial magnetic stimulation during isometric knee extensions of varying intensity. Superimposed twitch amplitude decreased linearly with increasing voluntary torque between 50 and 100% of mean maximal torque, allowing estimation of resting twitch amplitude and subsequent calculation of voluntary activation. There were no systematic differences for maximal voluntary activation within day (mean ±s.d. 90.9 ± 6.2 versus 90.7 ± 5.9%; P= 0.98) or between days (90.8 ± 6.0 versus 91.2 ± 5.7%; P= 0.92). Systematic bias and random error components of the 95% limits of agreement were 0.23 and 9.3% within day versus−0.38 and 7.5% between days. Voluntary activation was also determined immediately after a 2 min maximal voluntary isometric contraction; in four of these subjects, voluntary activation was determined 30 min after the sustained contraction. Immediately after the sustained isometric contraction, maximal voluntary activation was reduced from 91.2 ± 5.7 to 74.2 ± 12.0% ( P < 0.001), indicating supraspinal fatigue. After 30 min, voluntary activation had recovered to 85.4 ± 8.8% ( P= 0.39 versus baseline). These results demonstrate that transcranial magnetic stimulation enables reliable measurement of maximal voluntary activation and assessment of supraspinal fatigue of the knee extensors. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to elucidate the effects of cold water immersions (CWIs) following damaging exercise on the repeated bout effect (RBE). Sixteen males performed two bouts of drop jump exercise separated by 14-21 days. Participants were equally, but randomly assigned to either a CWI (12-min CWI at 15 degrees C) or control group (12-min seated rest). Treatments were given immediately after the first exercise bout, 24, 48 and 72 h post-exercise. No interventions were given following the second bout. Maximum voluntary contraction (MIVC), soreness (DOMS), creatine kinase (CK), thigh girth and range of motion (ROM) were recorded before and for 96 h following the initial and repeated bouts of damaging exercise. All variables, except ROM, showed a significant time effect (P < 0.01) indicating the presence of muscle damage following the initial bout; there were no differences between the CWI and control groups after the initial bout. Following the repeated bout of exercise there was a significant attenuation in the reduction of MIVC (P = 0.002) and a reduction in DOMS (P < 0.001), which is indicative of the RBE. There were no significant differences between groups following the repeated bout of damaging exercise. These data show that CWI had no effect following damaging exercise and did not inhibit the RBE. Despite CWI being used routinely, its efficacy remains unclear and there is a need to elucidate the benefits of this intervention on recovery and adaptation to provide practitioners with evidence based practice. [ABSTRACT FROM AUTHOR]

Synthetic microporous membranes with functional groups covalently attached were used to selectively separate β-lactoglobulin, BSA, and α-lactalbumin from rennet whey. The selectivity and membrane performance of strong (quaternary ammonium) and weak (diethylamine) ion-exchange membranes were studied using breakthrough curves, measurement of binding capacity, and protein composition of the elution fraction to determine the binding behavior of each membrane. When the weak and strong anion exchange membranes were saturated with whey, they were both selective primarily for β-lactoglobulin with less than 1% of the eluate consisting of α-lactalbumin or BSA. The binding capacity of a pure β-lactoglobulin solution was in excess of 1.5 mg/cm² of membrane. This binding capacity was reduced to approximately 1.2 mg/cm² when using a rennet whey solution (pH 6.4). This reduction in protein binding capacity can be explained by both the competitive effects of other whey proteins and the effect of ions present in whey. Using binary solution breakthrough curves and rennet whey breakthrough curves, it was shown that α-lactalbumin and BSA were displaced from the strong and weak anion exchange membranes by β-actoglobulin. Finally, the effect of ionic strength on the binding capacity of individual proteins for each membrane was determined by comparing model protein solutions in milk permeate (pH 6.4) and a 10 mM sodium phosphate buffer (pH 6.4). Binding capacities β-lactoglobulin, α-lactalbumin, and BSA in milk permeate were reduced by as much as 50%. This reduction in capacity coupled with the low binding capacity of current ion exchange membranes are 2 serious considerations for selectively separating complex and concentrated protein solutions. [ABSTRACT FROM AUTHOR]

Modern day health care should incorporate strategies for controlling both the cost and quality of clinical interventions, to ensure that care is evidence based, outcomes are monitored and any areas of poor practice are improved. An integrated care pathway for an area of vascular surgery was devised with these issues in mind. The chosen pathway was for patients undergoing surgery to remove atheromatous plaques from the carotid artery. The evidence base for the interventions detailed in the pathway are given and potential advantages and disadvantages of utilizing care pathways offered. Utilizing this form of structured care, health professionals may be able to ensure cost containment combined with high quality patient care. [ABSTRACT FROM AUTHOR]

Summary Background Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2–MT1-MMP–tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. Results All components of the MMP-2–TIMP-2–MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. Conclusion The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2–TIMP-2–MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs. [ABSTRACT FROM AUTHOR]

Dietary fat is fed to increase energy intake and provide fatty acids (FA) to support milk fat production. Oilseeds contain unsaturated FA that increase the risk for biohydrogenation-induced milk fat depression, but FA in whole cottonseed (WCS) are expected to be slowly released in the rumen and thus have a lower risk for biohydrogenation-induced milk fat depression. Our hypothesis was that increasing dietary WCS would increase milk fat yield by providing additional dietary FA without induction of milk fat depression. Four primiparous and 8 multiparous lactating Holstein cows, 136 ± 35 and 127 ± 4 DIM, respectively, were arranged in a replicated 4 × 4 Latin square design with 21-d periods. Treatments were WCS provided at 0%, 3.4%, 6.8%, and 9.9% of dietary dry matter, and WCS was substituted for cottonseed hulls and soybean meal to maintain dietary fiber and protein. Treatment did not change milk yield. There was a treatment-by-parity interaction for milk fat percent and yield with a quadratic decreased in primiparous cows but no effect of WCS in multiparous cows. Cottonseed linearly increased milk fat trans -10 18:1 in primiparous cows but not in multiparous cows. Increasing WCS increased milk preformed (18C) FA yield and partially overcame the trans- 10 18:1 inhibition of de novo FA synthesis in the primiparous cows. Apparent transfer of 18C FA from feed to milk decreased in all cows as WCS increased, but the magnitude of the change was greater in primiparous cows. Increasing WCS decreased total-tract apparent dry matter, organic matter, and neutral detergent fiber digestibility. There was no change in total FA digestibility. However, 18C FA digestibility tended to be decreased in both parities and 16C FA digestibility was quadratically increased in multiparous cows but not changed in primiparous cows. Total fecal flow of intact WCS increased as WCS level increased, but fecal flow of intact seeds as a percentage consumed was similar across treatments. Fecal flow of intact seeds was greater in multiparous cows (4.3% vs. 1.1% of consumed). Plasma concentrations of glucose, nonesterified FA, triglycerides, and insulin were not changed. However, plasma urea-N increased with increasing WCS. Plasma gossypol increased with WCS (0.08–1.15 µg/mL) but was well below expected toxic levels. In conclusion, WCS maintained milk and milk component yield when fed at up to 9.9% of the diet to multiparous cows without concerns of gossypol toxicity, but primiparous cows were more susceptible to biohydrogenation-induced milk fat depression in the current trial. This highlights the interactions of parity with diet composition when feeding rumen-available unsaturated fat to dairy cows. [ABSTRACT FROM AUTHOR]

Background: Rupture of an abdominal aortic aneurysm (AAA) carries a mortality rate of up to 90%. Matrix metalloproteinases (MMPs) play a fundamental role in aneurysm formation. Previous studies have suggested a systemic increase in proteolysis in patients with AAAs and MMPs have been shown to be elevated in the serum of these patients. However, no study as yet has demonstrated differences in asymptomatic and ruptured aneurysms. The aim of the study was to determine the MMP profiles of serum from patients presenting for elective and emergency aneurysm repair. Methods: Samples of venous blood were obtained intraoperatively from 61 patients undergoing elective repair of nonruptured AAA (n = 50, median age 71 years), or emergency repair (n = 11, age 72) of ruptured AAA. Serum was quantified for the concentration of MMPs-1, -2, -3, -9, -13, TIMP-1 and -2 utilizing ELISA. Results: There were no significant differences in MMPs-2,-3,-13 and TIMP levels in the serum of patients with nonruptured and ruptured AAA. Serum MMP-1 levels were significantly increased in rupture (10.36 ng mL-1 [IQR 5.94–15.94]versus 24.81 ng mL-1 [18.14–41.39], P < 0.0001). MMP-9 levels were six times higher in serum from ruptured compared with nonruptured AAA patients (19.13 ng mL-1 [9.27–34.24]versus 117.9 ng mL-1 [30.43–161.8], P = 0.0015). Conclusions: These data demonstrate that the serum MMP profile of patients with ruptured aneurysms is significantly different to patients with nonruptured AAA. Extension of these data may allow prediction of rupture rates from serum MMP levels. [ABSTRACT FROM AUTHOR]

SummaryBackground: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. Methods: Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10–5, 10–6 and 10–7 mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller’s elastin and van Gieson’s stain. Results: Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10–6 and 10–5 mol/l; this was significant at the latter concentration (P = 0·007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10–5 mol/l (P < 0·01). Conclusion: Marimastat significantly inhibited elastin degradation and active MMP-2 production within aortic organ cultures. [ABSTRACT FROM AUTHOR]

Post-activation potentiation ( PAP) is the increased involuntary muscle twitch response to stimulation following strong contraction. The enhancement to whole-body explosive muscular performance ( PE) after heavy-resistance exercise is often attributed to modulations in neuromuscular function that are proposed to reflect PAP, but the evidence to support this is equivocal. We assessed the neuromuscular basis of PE using transcranial magnetic stimulation ( TMS) of the primary motor cortex, and electrical stimulation of the femoral nerve. Eleven male athletes performed heavy-resistance exercise with measures of countermovement jump ( CMJ) pre- and 8 min post-exercise. Pre-exercise and after the final CMJ, single- and paired-pulse TMS were delivered during submaximal isometric knee-extensor contractions to measure corticospinal excitability, short-interval intracortical inhibition ( SICI), and intracortical facilitation ( ICF), with motor evoked potentials recorded from rectus femoris. Twitch responses to motor nerve stimulation during and post maximum-knee-extensor contractions were studied to quantify voluntary activation ( VA) and potentiated twitch ( Qtw,pot). The experimental protocol successfully induced PE (+4 ± 1% change in CMJ, P = 0.01), but no changes were observed for maximum voluntary force, VA, corticospinal excitability, SICI or ICF (all P > 0.05), and Qtw,pot declined ( P < 0.001). An enhancement of muscular performance after heavy-resistance exercise was not accompanied by PAP, or changes in measures of neuromuscular function. [ABSTRACT FROM AUTHOR]