Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and interestingly, a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.

The role of adenosine-related genes variants in susceptibility to essential hypertension

OBJECTIVE: To test markers within adenosine-related genes: A1 and A2a receptors (ADORA1, ADORA2a) and adenosine deaminase (ADA) for potential involvement in essential hypertension (EH). DESIGN: Case-control association study investigating gene variants for the ADORA1, ADORA2a and ADA genes. PARTICIPANTS: The study used a cohort of 249 unrelated hypertensive individuals who were diagnosed with hypertension, and an age, sex and ethnically matched group of 249 normotensive controls. RESULTS: The association analysis indicated that both allele and genotype frequencies did not differ significantly between the case and control groups (P > 0.05) for any of the markers tested. CONCLUSION: The adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives. However, involvement of these genes and the adenosine system cannot be conclusively excluded from essential hypertension pathogenesis as other gene variants may still be involved.

Clinically-indicated replacement versus routine replacement of peripheral venous catheters

BACKGROUND: US Centers for Disease Control guidelines recommend replacement of peripheral intravenous (IV) catheters no more frequently than every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bloodstream infection. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. This is an update of a review first published in 2010. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the PVD Specialised Register (December 2012) and CENTRAL (2012, Issue 11). We also searched MEDLINE (last searched October 2012) and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials with a total of 4895 patients were included in the review. Catheter-related bloodstream infection (CRBSI) was assessed in five trials (4806 patients). There was no significant between group difference in the CRBSI rate (clinically-indicated 1/2365; routine change 2/2441). The risk ratio (RR) was 0.61 but the confidence interval (CI) was wide, creating uncertainty around the estimate (95% CI 0.08 to 4.68; P = 0.64). No difference in phlebitis rates was found whether catheters were changed according to clinical indications or routinely (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39). This result was unaffected by whether infusion through the catheter was continuous or intermittent. We also analysed the data by number of device days and again no differences between groups were observed (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference in this outcome between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference (MD) -6.96, 95% CI -9.05 to -4.86; P ≤ 0.00001). AUTHORS' CONCLUSIONS: The review found no evidence to support changing catheters every 72 to 96 hours. Consequently, healthcare organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications. To minimise peripheral catheter-related complications, the insertion site should be inspected at each shift change and the catheter removed if signs of inflammation, infiltration, or blockage are present. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the PVD Specialised Register (December 2012) and CENTRAL (2012, Issue 11). We also searched MEDLINE (last searched October 2012) and clinical trials registries. SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials with a total of 4895 patients were included in the review. Catheter-related bloodstream infection (CRBSI) was assessed in five trials (4806 patients). There was no significant between group difference in the CRBSI rate (clinically-indicated 1/2365; routine change 2/2441). The risk ratio (RR) was 0.61 but the confidence interval (CI) was wide, creating uncertainty around the estimate (95% CI 0.08 to 4.68; P = 0.64). No difference in phlebitis rates was found whether catheters were changed according to clinical indications or routinely (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39). This result was unaffected by whether infusion through the catheter was continuous or intermittent. We also analysed the data by number of device days and again no differences between groups were observed (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference in this outcome between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference (MD) -6.96, 95% CI -9.05 to -4.86; P ≤ 0.00001). AUTHORS' CONCLUSIONS: The review found no evidence to support changing catheters every 72 to 96 hours. Consequently, healthcare organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications. To minimise peripheral catheter-related complications, the insertion site should be inspected at each shift change and the catheter removed if signs of inflammation, infiltration, or blockage are present.

Isoenergetic replacement of dietary saturated with monounsaturated fat via macadamia nuts enhances endothelial function in overweight subjects

Background & aims: - Excess adiposity (overweight) is one of numerous risk factors for cardiometabolic disease. Most risk reduction strategies for overweight rely on weight loss through dietary energy restriction. However, since the evidence base for long-term successful weight loss interventions is scant, it is important to identify strategies for risk reduction independent of weight loss. The aim of this study was to compare the effects of isoenergetic substitution of dietary saturated fat (SFA) with monounsaturated fat (MUFA) via macadamia nuts on coronary risk compared to usual diet in overweight adults. Methods: - A randomised controlled trial design, maintaining usual energy intake, but manipulating dietary lipid profile in a group of 64 (54 female, 10 male) overweight (BMI > 25), otherwise healthy, subjects. For the intervention group, energy intakes of usual (baseline) diets were calculated from multiple 3 day diet diaries, and SFA was replaced with MUFA (target: 50%E from fat as MUFA) by altering dietary SFA sources and adding macadamia nuts to the diet. Both control and intervention groups received advice on national guidelines for physical activity and adhered to the same protocol for diet diary record keeping and trial consultations. Anthropometric and clinical measures were taken at baseline and at 10 weeks. Results: A significant increase in brachial artery flow-mediated dilation (p < 0.05) was seen in the monounsaturated diet group at week 10 compared to baseline. This corresponded to significant decreases in waist circumference, total cholesterol (p < 0.05), plasma leptin and ICAM-1 (p < 0.01). Conclusions: - In patient subgroups where adherence to dietary energy-reduction is poor, isoenergetic interventions may improve endothelial function and other coronary risk factors without changes in body weight. This trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12607000106437).

Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility

Typical migraine is a complex neurological disorder comprised of two main subtypes: migraine with (MA) and without aura (MO). The disease etiology is still unclear, but family studies provide strong evidence that defective genes play an important role. Familial hemiplegic migraine (FHM) is a very rare and severe subtype of MA. It has been proposed that FHM and MA may have a similar genetic etiology. Therefore, genetic studies on FHM provide a useful model for investigating the more prevalent types of typical migraine. FHM in some families has been shown to be caused by mutations in a brain-specific P/Q-type calcium channel alpha1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a report of a CACNA1A mutation being associated with MA in a patient from a family with predominant FHM. We have previously demonstrated suggestive linkage of typical migraine in a large Australian family to the FHM region on chromosome 19p13. These findings suggest that CACNA1A may also be implicated in the etiology of typical migraine in this pedigree. To investigate this possibility, we sequenced two patients carrying the critical susceptibility haplotype surrounding CACNA1A. No disease-causing mutations or polymorphisms were revealed in any of the 47 exons screened. To determine whether the CACNA1A gene was implicated in typical migraine susceptibility in the general Caucasian population, we also analyzed 82 independent pedigrees and a large case control group. We did not detect any linkage or association in these groups and conclude that if CACNA1A plays a role in typical migraine, it does not confer a major effect on the disease.

Simultaneous determination of aldrin, dieldrin, endrin, heptachlor, and p,p'-DDT in medicinal plant extracts using a novel high performance liquid chromatography method

A high performance liquid chromatographic method for the simultaneous determination of five organochlorine pesticides (aldrin, p,p’-DDT, dieldrin, endrin, and heptachlor) was developed. The method was used to determine the levels of these pesticides in medicinal plant samples. Analysis was carried out using a Merck LiChrospher 100 RP C18 (5 μm) column with a gradient solvent system of acetonitrile-water and PDA UV detection (224 nm). Quantification was carried out by the external standard method. The limit of detection for the utilized method was below the local legal limits (ANZFA) for similar plant materials for all 5 pesticides excepting endrin. Medicinal plant extracts were further analyzed by conventional GC-ECD and GC-NPD means using SPE and GPC cleanup as required.

The B subunit of coagulation factor XIII is linked to renin and the Duffy blood group to α-spectrin on human chromosome 1

Family linkage studies were used to detect two linkage relationships on human chromosome 1. The B subunit of coagulation factor XIII showed significant linkage to renin with a maximum lod score of 5.071 at a distance of 10 cM. Significant linkage was also shown between the Duffy blood group and α-spectrin with linkage results giving a combined lod score of 3.194 at 5 cM.

Baseline study of alcohol dependence among general drivers and drunk driving offenders in Guangzhou, China

This study aimed to investigate drink driving in a sample of general drivers and convicted drunk driving offenders in Guangzhou, China. The study also aimed to explore some potential factors that impact on alcohol-related driving behaviour. Samples of 406 general drivers and 101 drunk driving offenders were recruited between May and October 2012. A survey was used to collect information about demographic characteristics, knowledge, attitudes and practices related to drink driving. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess possible drinking problems. The average age reported for starting to drink alcohol for both groups of participants was around 19 years old. The mean AUDIT score of general drivers was 7.4 (SD = 5.4) representing a low level of alcohol problems, and for convicted drunk driving offenders was 11.1 (SD = 5.9) representing a medium level of alcohol problems (significant difference between means, t = 5.75, p < 0.001). AUDIT scores indicated that a substantial proportion (65%) of the offenders had medium to high levels of alcohol use disorders, compared with 38.5% among general drivers. Offenders who knew the drunk driving legal limit had a lower AUDIT score (M = 9.8, SD = 5.16) than those who did not know it (M = 12.2, SD = 6.257, t = -1.987. p = 0.05). In addition, offenders who were novice drivers (licensed less than 2 years) had a higher AUDIT score (M = 16.4, SD = 7.6) than the other three driver experience categories used.

Randomized controlled trial : a randomized controlled clinical trial comparing a remineralizing paste with an antibacterial gel to prevent early childhood caries

PURPOSE: The purpose of this study was to compare twice daily tooth-brushing using 0.304 percent fluoride toothpaste alone with: (1) twice daily tooth-brushing plus once daily 10% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste; and (2) twice daily tooth-brushing plus once daily 0.12% chlorhexidine gel (CHX) for reducing early childhood caries (ECC) and mutans streptococci (MS) colonization. METHODS: Subjects (n=622) recruited at birth were randomized to receive either CPP-ACP or CHX or no product (study control [SC]). All children were examined at 6, 12, and 18 months old in their homes, and at 24 months old in a community dental clinic. RESULTS: At 24 months old, the caries incidence was 1% (2/163) in CPP-ACP, 2% (4/180) in CHX, and 2% (3/188) in SC groups. In children who were previously MS colonized at 12 and 18 months old, 0% (0/11) and 5% (3/63), respectively, of the CPP-ACP group remained MS-positive versus 22% (2/9) and 72% (18/25) in CHX and 16% (4/25) and 50% (7/14) in SC groups (P<.001). CONCLUSIONS: There is insufficient evidence to justify the daily use of casein phosphopeptide-amorphous calcium phosphate or chlorhexidine gel to control early childhood caries.

A randomised, controlled clinical trial comparing chlorhexidine gel and low-dose fluoride toothpaste to prevent early childhood caries

Objectives This randomised, controlled trial compared the effectiveness of 0.12% chlorhexidine (CHX) gel and 304% fluoride toothpaste to prevent early childhood caries (ECC) in a birth cohort by 24 months. Methods The participants were randomised to receive either (i) twice daily toothbrushing with toothpaste and once daily 0.12% CHX gel (n = 110) or (ii) twice daily toothbrushing with toothpaste only (study controls) (n = 89). The primary outcome measured was caries incidence and the secondary outcome was percentage of children with mutans streptococci (MS). All mothers were contacted by telephone at 6, 12, and 18 months. At 24 months, all children were examined at a community dental clinic. Results At 24 months, the caries prevalence was 5% (3/61) in the CHX and 7% (4/58) in the controls (P = 0.7). There were no differences in percentages of MS-positive children between the CHX and control groups (54%vs 53%). Only 20% applied the CHX gel once daily and 80% less than once daily. Conclusions Toothbrushing using 304% fluoride toothpaste with or without the application of chlorhexidine gel (0.12%) reduces ECC from 23% found in the general community to 5–7%. The lack of effect with chlorhexidine is likely to be due to low compliance.

Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was test by χ analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P<0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P<0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, α2- and β1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension. 5. The present results suggest that genetic variant(s) in close linkage disequilibrium with polymorphisms at INSR and DCP1 may be involved in part in the aetiology of essential hypertension.

Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age ≥50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (χ2 = 4.8, P<0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p 13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.

Evidence for allelic association of the dopamine β-hydroxylase gene (DBH) with susceptibility to typical migraine

Migraine is a debilitating neurological disorder characterized by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains mutations responsible for familial hemiplegic migraine, a rare and severe subtype of migraine. There is also evidence to suggest that serotonin- and dopamine-related genes may be involved in the pathogenesis of migraine. This study employed a linkage and association approach to investigate neurotransmitter-related migraine candidate genes. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs and 182 control individuals. In addition, an independent sample of 82 families affected with migraine was examined. Unrelated case-control association analysis of a DBH intragenic dinucleotide polymorphism indicated altered allelic distribution between migraine and control groups (L2=16.53, P=0.019). Furthermore, the transmission/disequilibrium test, which was implemented on the family data, also indicated distortion of allele transmission for the same DBH marker (L2=4.44, P=0.035). Together, these results provide evidence for allelic association of the DBH gene with typical migraine susceptibility (Fisher's combined P value=0.006) and indicate that further research into the role of the DBH gene in the etiology of migraine is warranted.

Effects of hyperbaric oxygen and inducible nitric oxide synthase inhibitor treatment on femoral head osteonecrosis in a rat model

Introduction: Apoptosis is the final destiny of many cells in the body, though this process has been observed in some pathological processes. One of these pathological processes is femoral head non-traumatic osteonecrosis. Among many pro/anti-apoptotic factors, nitric oxide has recently been an area of further interest. Osteocyte apoptosis and its relation to pro-apoptotic action invite further research, and the inducible form of nitric oxide synthase (iNOS)—which produces a high concentration of nitric oxide—has been flagged. The aim of this study was to investigate the effect of hyperbaric oxygen (HBO) and inducible NOS suppressor (Aminoguanidine) in prevention of femoral head osteonecrosis in an experimental model of osteonecrosis in spontaneous hypertensive rats (SHRs). Methods: After animal ethic approval 34 SHR rats were divided into four groups. Ten rats were allocated to the control group without any treatment, and eight rats were allocated to three treatment groups namely: HBO, Aminoguanidine (AMG), and the combination of HBO and AMG treatments (HBO+AMG). The HBO group received 250 kPa of oxygen via hyperbaric chamber for 30 days started at their 5th week of life; the AMG group received 1mg/ml of AMG in drinking water from the fifth week till the 17th week of life; and the last group received a combination of these treatments. Rats were sacrificed at the end of the 17th week of life and both femurs were analysed for evidence of osteonecrosis using Micro CT scan and H&E staining. Also, osteocyte apoptosis and the presence of two different forms of NOS (inducible (iNOS) and endothelial (eNOS)) were analysed by immunostaining and apoptosis staining (Hoechst and TUNEL). Results: Bone morphology of metaphyseal and epiphyseal area of all rats were investigated and analysed. Micro CT findings revealed significantly higher mean fractional trabecular bone volume (FBV) of metaphyseal area in untreated SHRs compared with all other treatments (HBO, P<0.05, HBO+AMG, P<0.005, and AMG P<0.001). Bone surface to volume ratio also significantly increased with HBO+AMG and AMG treatments when compared with the control group (18.7 Vs 20.8, P<0.05, and 18.7 Vs 21.1, P<0.05). Epiphyseal mean FBV did not change significantly among groups. In the metaphyseal area, trabecular thickness and numbers significantly decreased with AMG treatment, while trabecular separation significantly increased with both AMG and HBO+AMG treatment. Histological ratio of no ossification and osteonecrosis was 37.5%, 43.7%, 18.7% and 6.2% of control, HBO, HBO+AMG and AMG groups respectively with only significant difference observed between HBO and AMG treatment (P<0.01). High concentration of iNOS was observed in the region of osteonecrosis while there was no evidence of eNOS activity around that region. In comparison with the control group, the ratio of osteocyte apoptosis significantly reduced in AMG treatment (P<0.005). We also observed significantly fewer apoptotic osteocytes in AMG group comparing with HBO treatment (P<0.05). Conclusion: None of our treatments prevents osteonecrosis at the histological or micro CT scan level. High concentration of iNOS in the region of osteonecrosis and significant reduction of osteocyte apoptosis with AMG treatment were supportive of iNOS modulating osteocyte apoptosis in SHRs.

Malnutrition in Parkinson's disease and an individualised approach to its management

It has been reported that poor nutritional status, in the form of weight loss and resulting body mass index (BMI) changes, is an issue in people with Parkinson's disease (PWP). The symptoms resulting from Parkinson's disease (PD) and the side effects of PD medication have been implicated in the aetiology of nutritional decline. However, the evidence on which these claims are based is, on one hand, contradictory, and on the other, restricted primarily to otherwise healthy PWP. Despite the claims that PWP suffer from poor nutritional status, evidence is lacking to inform nutrition-related care for the management of malnutrition in PWP. The aims of this thesis were to better quantify the extent of poor nutritional status in PWP, determine the important factors differentiating the well-nourished from the malnourished and evaluate the effectiveness of an individualised nutrition intervention on nutritional status. Phase DBS: Nutritional status in people with Parkinson's disease scheduled for deep-brain stimulation surgery The pre-operative rate of malnutrition in a convenience sample of people with Parkinson's disease (PWP) scheduled for deep-brain stimulation (DBS) surgery was determined. Poorly controlled PD symptoms may result in a higher risk of malnutrition in this sub-group of PWP. Fifteen patients (11 male, median age 68.0 (42.0 – 78.0) years, median PD duration 6.75 (0.5 – 24.0) years) participated and data were collected during hospital admission for the DBS surgery. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference, waist circumference, body mass index (BMI)) were taken, and body composition was measured using bioelectrical impedance spectroscopy (BIS). Six (40%) of the participants were malnourished (SGA-B) while 53% reported significant weight loss following diagnosis. BMI was significantly different between SGA-A and SGA-B (25.6 vs 23.0kg/m 2, p<.05). There were no differences in any other variables, including PG-SGA score and the presence of non-motor symptoms. The conclusion was that malnutrition in this group is higher than that in other studies reporting malnutrition in PWP, and it is under-recognised. As poorer surgical outcomes are associated with poorer pre-operative nutritional status in other surgeries, it might be beneficial to identify patients at nutritional risk prior to surgery so that appropriate nutrition interventions can be implemented. Phase I: Nutritional status in community-dwelling adults with Parkinson's disease The rate of malnutrition in community-dwelling adults (>18 years) with Parkinson's disease was determined. One hundred twenty-five PWP (74 male, median age 70.0 (35.0 – 92.0) years, median PD duration 6.0 (0.0 – 31.0) years) participated. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference (MAC), calf circumference, waist circumference, body mass index (BMI)) were taken. Nineteen (15%) of the participants were malnourished (SGA-B). All anthropometric indices were significantly different between SGA-A and SGA-B (BMI 25.9 vs 20.0kg/m2; MAC 29.1 – 25.5cm; waist circumference 95.5 vs 82.5cm; calf circumference 36.5 vs 32.5cm; all p<.05). The PG-SGA score was also significantly lower in the malnourished (2 vs 8, p<.05). The nutrition impact symptoms which differentiated between well-nourished and malnourished were no appetite, constipation, diarrhoea, problems swallowing and feel full quickly. This study concluded that malnutrition in community-dwelling PWP is higher than that documented in community-dwelling elderly (2 – 11%), yet is likely to be under-recognised. Nutrition impact symptoms play a role in reduced intake. Appropriate screening and referral processes should be established for early detection of those at risk. Phase I: Nutrition assessment tools in people with Parkinson's disease There are a number of validated and reliable nutrition screening and assessment tools available for use. None of these tools have been evaluated in PWP. In the sample described above, the use of the World Health Organisation (WHO) cut-off (≤18.5kg/m2), age-specific BMI cut-offs (≤18.5kg/m2 for under 65 years, ≤23.5kg/m2 for 65 years and older) and the revised Mini-Nutritional Assessment short form (MNA-SF) were evaluated as nutrition screening tools. The PG-SGA (including the SGA classification) and the MNA full form were evaluated as nutrition assessment tools using the SGA classification as the gold standard. For screening, the MNA-SF performed the best with sensitivity (Sn) of 94.7% and specificity (Sp) of 78.3%. For assessment, the PG-SGA with a cut-off score of 4 (Sn 100%, Sp 69.8%) performed better than the MNA (Sn 84.2%, Sp 87.7%). As the MNA has been recommended more for use as a nutrition screening tool, the MNA-SF might be more appropriate and take less time to complete. The PG-SGA might be useful to inform and monitor nutrition interventions. Phase I: Predictors of poor nutritional status in people with Parkinson's disease A number of assessments were conducted as part of the Phase I research, including those for the severity of PD motor symptoms, cognitive function, depression, anxiety, non-motor symptoms, constipation, freezing of gait and the ability to carry out activities of daily living. A higher score in all of these assessments indicates greater impairment. In addition, information about medical conditions, medications, age, age at PD diagnosis and living situation was collected. These were compared between those classified as SGA-A and as SGA-B. Regression analysis was used to identify which factors were predictive of malnutrition (SGA-B). Differences between the groups included disease severity (4% more severe SGA-A vs 21% SGA-B, p<.05), activities of daily living score (13 SGA-A vs 18 SGA-B, p<.05), depressive symptom score (8 SGA-A vs 14 SGA-B, p<.05) and gastrointestinal symptoms (4 SGA-A vs 6 SGA-B, p<.05). Significant predictors of malnutrition according to SGA were age at diagnosis (OR 1.09, 95% CI 1.01 – 1.18), amount of dopaminergic medication per kg body weight (mg/kg) (OR 1.17, 95% CI 1.04 – 1.31), more severe motor symptoms (OR 1.10, 95% CI 1.02 – 1.19), less anxiety (OR 0.90, 95% CI 0.82 – 0.98) and more depressive symptoms (OR 1.23, 95% CI 1.07 – 1.41). Significant predictors of a higher PG-SGA score included living alone (β=0.14, 95% CI 0.01 – 0.26), more depressive symptoms (β=0.02, 95% CI 0.01 – 0.02) and more severe motor symptoms (OR 0.01, 95% CI 0.01 – 0.02). More severe disease is associated with malnutrition, and this may be compounded by lack of social support. Phase II: Nutrition intervention Nineteen of the people identified in Phase I as requiring nutrition support were included in Phase II, in which a nutrition intervention was conducted. Nine participants were in the standard care group (SC), which received an information sheet only, and the other 10 participants were in the intervention group (INT), which received individualised nutrition information and weekly follow-up. INT gained 2.2% of starting body weight over the 12 week intervention period resulting in significant increases in weight, BMI, mid-arm circumference and waist circumference. The SC group gained 1% of starting weight over the 12 weeks which did not result in any significant changes in anthropometric indices. Energy and protein intake (18.3kJ/kg vs 3.8kJ/kg and 0.3g/kg vs 0.15g/kg) increased in both groups. The increase in protein intake was only significant in the SC group. The changes in intake, when compared between the groups, were no different. There were no significant changes in any motor or non-motor symptoms or in "off" times or dyskinesias in either group. Aspects of quality of life improved over the 12 weeks as well, especially emotional well-being. This thesis makes a significant contribution to the evidence base for the presence of malnutrition in Parkinson's disease as well as for the identification of those who would potentially benefit from nutrition screening and assessment. The nutrition intervention demonstrated that a traditional high protein, high energy approach to the management of malnutrition resulted in improved nutritional status and anthropometric indices with no effect on the presence of Parkinson's disease symptoms and a positive effect on quality of life.