Purpose: The purpose of this project was to look at the costs of individuals with Alzheimer’s disease and related dementias (ADRD), ALS, and MS in long stay home care in Ontario, Canada. The specific goals were to produce estimates of costs for these individuals, as well as identify clinical and personal characteristics associated with these costs. This project also tested the effectiveness of the Resource Utilization Group for home care case-mix system for use in these special populations. Methods: This project was conducted using a secondary analysis of assessment data from the Canadian Staff Time Resource Intensity Verification Project, a 13-week study of home care costs (N=435 141). The project was guided by the Andersen and Newman (1973) framework for healthcare resource utilization. Descriptive characteristics and mean costs were produced using bivariate frequency and means procedures for each of three conditions. Predictors of costs were identified for each of the three neurological conditions through multivariate regression analysis conducted separately for each condition. In total 41 independent variables were included into the bivariate and multivariate analyses. The dependent variable was the total weekly formal and informal home care costs across all multivariate analyses. Results: In total, ADRD, ALS, or MS diagnoses were present in 16% of the assessments. The mean costs for the three conditions combined were $594.81. The mean costs for ADRD, ALS, and MS were $593.32, $898.41, and $574.92, respectively. Characteristics that were predictive of cost across all conditions included the Resource Utilization Group for home care case-mix system, ADL functionality, IADL functionality, cognitive performance, unsteady gait, stair use, difficulty swallowing, respiratory challenges, and bowel incontinence. The Resource Utilization Group for home care case-mix system had the highest level of explained variance of any single item tested in this project across all conditions. However, other clinical characteristics also contributed substantial levels of explained variance to the models for each of the three conditions. Conclusions: The findings from this project suggest that although diagnosis of ADRD, ALS, and/or MS can describe cost, clinical characteristics are the most important predictors of costs for individuals with these conditions. In addition, the Resource Utilization Group for home care case-mix system can adequately predict costs of individuals with these conditions. The addition of some clinical characteristics would likely improve the predictive abilities of the Resource Utilization Group for home care case-mix system.

Amyotrophic lateral sclerosis (ALS) is a debilitating, incurable, neurodegenerative disease characterized by degradation of motor neurons leading to paralysis and ultimately death in ~3-5 years. Approximately 10% of ALS cases have a dominant inheritance pattern, termed familial ALS (fALS). Mutations in the gene encoding the dimeric superoxide scavenger Cu, Zn superoxide dismutase (SOD), were found to be associated with ~20% of fALS cases. Over 110 predominantly missense SOD mutations lead to fALS by an unknown mechanism; however, it is thought that mutant SOD acquires a toxic gain of function. Mice as well as human post mortem studies have identified mutant SOD-rich aggregates in affected neurons, leading to the hypothesis that mutations in SOD increase the tendency of the protein to form toxic aggregates. SOD has a complex maturation process whereby the protein is synthesized in an apo or demetalated state, followed by formation of an intramolecular disulfide bond and binding of Zn2+ and Cu2+. Each of these post-translational modifications increases the stability of the protein. SOD has been shown to aggregate more readily from destabilized immature states, including the apo state both with and without the disulfide bond, highlighting the importance of these states. Thermal unfolding monitored by differential scanning calorimetry (DSC) and chemical denaturation monitored by optical spectroscopy were used to elucidate the folding mechanism and stability of both the apo SOD disulfide-intact and disulfide-reduced states. Chemically and structurally diverse fALS-associated mutants were investigated to gain insights into why mutant SODs may be more prone to misfold and ultimately aggregate. The mutations were introduced into a pseudo wild-type (PWT) background lacking free cysteines, resulting in highly reversible unfolding amenable to accurate thermodynamic analysis. Similarly to what was previously described for fully metallated (holo) SODs, chemical denaturation of the apo disulfide-intact SODs is well described by a 3-state dimer mechanism with native dimer, monomeric intermediate and unfolded monomer populated at equilibrium. Although removal of metals has a relatively small effect on the stability of the dimer interface, the stability of the monomer intermediate is dramatically reduced. Thermal unfolding of some disulfide-intact apo SOD mutants as well as PWT is well described by a 2-state dimer mechanism, while others unfold via a 3-state mechanism similar to chemical denaturation. All but one of the studied disulfide-intact apo mutations are destabilizing as evidenced by reductions in ΔG of unfolding. Additionally, several mutants show an increased tendency to aggregate in thermal unfolding studies through increased ratios of van’t Hoff to calorimetric enthalpy (HvH/ Hcal ). The effects of the mutations on dimer interface stability in the apo disulfide-intact form were further investigated by isothermal titration calorimetry (ITC) which provided a quantitative measure of the dissociation constant of the dimer (Kd). ITC results revealed that disulfide-intact apo SOD mutants generally have increased Kd values and hence favor dimer dissociation to the less stable monomer which has been proposed to be a precursor to toxic aggregate formation. Reduction of the disulfide bond in apo SOD leads to marked destabilization of the dimer interface, and both thermal unfolding and chemical denaturation of PWT and mutants are well described by a 2-state monomer unfolding mechanism. Most mutations destabilize the disulfide-reduced apo SOD to such an extent that the population of unfolded monomer under physiological conditions exceeds 50%. The disulfide-reduced apo mutants show increased tendency to aggregate relative to PWT in DSC experiments through increased HvH /Hcal, low or negative change in heat capacity of unfolding and/or decreased unfolding reversibility. Further evidence of enhanced aggregation tendency of disulfide-reduced apo mutants was derived from analytical ultracentrifugation sedimentation equilibrium experiments that revealed the presence of weakly associated aggregates. Overall, the results presented here provide novel insights into SOD maturation and the possible impact of stability on aggregation.

Bakgrund: Amyotrofisk lateral skleros (ALS) är en obotlig neurologisk sjukdom som gör att nervceller dör. Det gör att muskler förtvinar och efter en tids sjukdom blir individen successivt förlamad. Således drabbas även tal- samt sväljförmåga som gör det svårt att tala och äta. Sjukdomen påverkar inte den ALS-drabbades intellekt eller tankeförmåga men inverkar psykiskt till följd av konsekvenserna av att drabbas av sjukdomen. Årligen får cirka 200 personer i Sverige diagnosen ALS som vanligen leder till döden inom tre till fem år efter diagnos. Syfte: Syftet med studien var att belysa personers upplevelser av att leva med ALS Metod: En kvalitativ studie valdes med inriktning mot att granska självbiografier skrivna av författare diagnostiserade med ALS. Resultat: Studiens resultat visade att sjukdomen begränsade individernas vardagliga liv men även skapade möjligheter till personlig utveckling. Det upplevdes smärtsamt att mista kroppsfunktioner och bli beroende av hjälp från andra personer. Sjukdomen skapade ett kaos av känslor och medförde att de lärde sig att leva på ett nytt sätt. De uppskattade vardagssituationer med skratt och närhet samtidigt som tankar på döden ständigt återkom. Slutsats: För att vårda dessa patienter, eller patienter under liknande omständigheter, behövs förståelse, respekt, lyhördhet och empati från sjukvårdspersonalen. / Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurological disorder that causes nerve cells to die. This leads to muscle atrophy and the diseased becomes progressively paralyzed. The disease is also affecting speech and swallowing. ALS doesn’t affect the intellectual ability but the person is psychologically affected. ALS annually effects 200 people in Sweden and leads to death within three to five years after the diagnosis. Aim: The purpose of this study was to develop understanding of patients by illuminating the ALS-affected people’s experience to live with the illness. Methods: It was a qualitative study aimed at examining autobiographies written by authors diagnosed with ALS. Results: The results showed that the disease gave individuals considerable limitations to everyday life but also opportunities for personal development. It felt painful for patients to gradually lose body functions and therefore become dependent on help from others. The disease created a chaos of emotions and meant to learn a new way of life. They learned to appreciate everyday situations with laughter and closeness while thoughts of death were recurrent. Conclusion: To care for these patients, or patients in similar circumstances, it’s necessary for health care professionals to meet them with understanding, respect, sensitivity and empathy.

Bakgrund: Amyotrofisk lateralskleros (ALS) är en motorneuron sjukdom som bryter ner kroppens muskler. Detta försvagar de kroppsliga funktionerna. För att klara av sin vardag ökar då beroendet av hjälp från både hjälpmedel och människor. Syfte: Syftet var att belysa personers upplevelser av att vara beroende av hjälp vid sjukdomen ALS. Metod: En kvalitativ innehållsanalys har använts och materialet hämtats från bloggar och biografier som beskriver personers liv med ALS. Resultat: I resultatet beskrivs följande kategorier: Att vara beroende av hjälp från hjälpmedel, att vara beroende av hjälp från närstående, att vara beroende av hjälp från utomstående och att vara beroende av hjälp från samhället. Diskussion: Det huvudsakliga fyndet var upplevelsen av att inte längre vara delaktig i sitt eget liv. En stor rädsla fanns över att någon främmande skulle ta hand om ens behov och en känsla av underlägsenhet kunde uppstå. Missnöje med samhällets hjälp och känslan av att vara ifrågasatt förekom. / Background: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that breaks down the muscles of the body. This debilitates the functions of the body. In order to get through everyday life the dependence on help from both aids and people increases. Aim: The aim is to elucidate experiences of being dependent on help because of ALS. Method: A qualitative content analysis was used and the data was gathered from blogs and biographies describing persons living with ALS. Results: The result describes following categories: Being dependent on help from aids, relatives, formal helpers and the community. Discussion: The main findings were that persons could feel powerlessness and as if they no longer were involved in their own lives. There was a fear that strangers would involve and take care of the personal needs and because of that feelings of inferiority could occur. Several persons were dissatisfied with the lack of help from the community and the feeling of being questioned often came up.

Amyotrophic lateral sclerosis (ALS) is a debilitating, incurable, neurodegenerative disease characterized by degradation of motor neurons leading to paralysis and ultimately death in ~3-5 years. Approximately 10% of ALS cases have a dominant inheritance pattern, termed familial ALS (fALS). Mutations in the gene encoding the dimeric superoxide scavenger Cu, Zn superoxide dismutase (SOD), were found to be associated with ~20% of fALS cases. Over 110 predominantly missense SOD mutations lead to fALS by an unknown mechanism; however, it is thought that mutant SOD acquires a toxic gain of function. Mice as well as human post mortem studies have identified mutant SOD-rich aggregates in affected neurons, leading to the hypothesis that mutations in SOD increase the tendency of the protein to form toxic aggregates. SOD has a complex maturation process whereby the protein is synthesized in an apo or demetalated state, followed by formation of an intramolecular disulfide bond and binding of Zn2+ and Cu2+. Each of these post-translational modifications increases the stability of the protein. SOD has been shown to aggregate more readily from destabilized immature states, including the apo state both with and without the disulfide bond, highlighting the importance of these states. Thermal unfolding monitored by differential scanning calorimetry (DSC) and chemical denaturation monitored by optical spectroscopy were used to elucidate the folding mechanism and stability of both the apo SOD disulfide-intact and disulfide-reduced states. Chemically and structurally diverse fALS-associated mutants were investigated to gain insights into why mutant SODs may be more prone to misfold and ultimately aggregate. The mutations were introduced into a pseudo wild-type (PWT) background lacking free cysteines, resulting in highly reversible unfolding amenable to accurate thermodynamic analysis. Similarly to what was previously described for fully metallated (holo) SODs, chemical denaturation of the apo disulfide-intact SODs is well described by a 3-state dimer mechanism with native dimer, monomeric intermediate and unfolded monomer populated at equilibrium. Although removal of metals has a relatively small effect on the stability of the dimer interface, the stability of the monomer intermediate is dramatically reduced. Thermal unfolding of some disulfide-intact apo SOD mutants as well as PWT is well described by a 2-state dimer mechanism, while others unfold via a 3-state mechanism similar to chemical denaturation. All but one of the studied disulfide-intact apo mutations are destabilizing as evidenced by reductions in ΔG of unfolding. Additionally, several mutants show an increased tendency to aggregate in thermal unfolding studies through increased ratios of van’t Hoff to calorimetric enthalpy (HvH/ Hcal ). The effects of the mutations on dimer interface stability in the apo disulfide-intact form were further investigated by isothermal titration calorimetry (ITC) which provided a quantitative measure of the dissociation constant of the dimer (Kd). ITC results revealed that disulfide-intact apo SOD mutants generally have increased Kd values and hence favor dimer dissociation to the less stable monomer which has been proposed to be a precursor to toxic aggregate formation. Reduction of the disulfide bond in apo SOD leads to marked destabilization of the dimer interface, and both thermal unfolding and chemical denaturation of PWT and mutants are well described by a 2-state monomer unfolding mechanism. Most mutations destabilize the disulfide-reduced apo SOD to such an extent that the population of unfolded monomer under physiological conditions exceeds 50%. The disulfide-reduced apo mutants show increased tendency to aggregate relative to PWT in DSC experiments through increased HvH /Hcal, low or negative change in heat capacity of unfolding and/or decreased unfolding reversibility. Further evidence of enhanced aggregation tendency of disulfide-reduced apo mutants was derived from analytical ultracentrifugation sedimentation equilibrium experiments that revealed the presence of weakly associated aggregates. Overall, the results presented here provide novel insights into SOD maturation and the possible impact of stability on aggregation.

Amyotrofisk Lateral Skleros, ALS, är en neurologisk sjukdom vilken leder till att samtliga kroppens muskler förtvinas och dör. Då sjukdomen saknar bot blir all behandling symptomatisk och individuellt anpassad för varje enskild persons behov. I denna systematiska litteraturstudie har det sökts efter olika sätt att stötta denna patientgrupp då syftet att belysa hur vi som personal kan hjälpa och stötta personer med ALS relaterad dysfagi och andningsproblem till en så bra tillvaro som möjligt skulle belysas.Författarna har funnit att omvårdnaden sällan sätts i fokus. Det är istället de lösningar som tar bort symtomet som fått fokus i flertalet av de artiklar som granskats. Att hjälpa dessa personer till trygga och oberoende människor som kan fortsätta att leva istället för som många av artiklarna visade då det gjordes insatser som ledde till att personerna blev mer bundna till sina anhöriga och sina vårdare.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease. Despite the debilitating nature of this disease, some evidence suggests patients maintain their quality of life (QOL). Caregivers, on the other hand, experience decreased QOL. Evidence suggests existential aspects of well-being such as purpose in life (PIL) may be unique and stable sources of well-being for patients and caregivers. Furthermore, patients’ and caregivers’ well-being may impact one another. The present study examined the variance structure, trajectory, and dyadic relationship of PIL and QOL in patients with ALS and their caregivers (N = 110 dyads). Data from the Seattle ALS Patient Profile Project were utilized; PIL and QOL were assessed seven times, over eighteen months. PIL was more stable than QOL and therefore a psychological resource for patients and caregivers. PIL and QOL declined with time and disease severity. Individual differences in proximity to diagnosis and death moderated within-individual change. Decline was more rapid following diagnosis and approaching death, suggesting these are critical periods in which individuals need increased support. Well-being within the dyad was interrelated. Average QOL was similar across dyads. PIL within the dyad changed together over time. Dyadic relationships may reflect similar life conditions and a shared disease experience.

Amyotrofisk lateralskleros (ALS) är en obotlig, neurologisk sjukdom som karaktäriseras av en progressiv nedbrytning av det motoriska nervsystemet. Symtomen är tilltagande muskelsvaghet som slutligen orsakar förlamning och andningssvikt. Överlevnadstiden från sjukdomens debut är två till fem år. Det finns i dagsläget ingen botande behandling mot ALS, istället läggs fokus på att lindra symtom. Syftet med studien var att belysa livskvalitét och välbefinnande hos patienter med den obotliga sjukdomen ALS. Metoden som användes var en litteraturstudie baserad på tretton vetenskapliga artiklar som analyserades och sammanställdes. I resultatet framkom fyra teman; Betydelsen av fysisk försämring och förlust av kroppslig funktion, Betydelsen av stöd från familj, vänner och vårdgivare, Betydelsen av att leva i nuet och blunda för framtiden samt Betydelsen av att känna hopp och upprätthålla en positiv syn på livet. Det är angeläget att det genomförs fler kvalitativa studier som undersöker patienters individuella upplevelser av att leva med sjukdomen ALS. / Amyotrophic lateral sclerosis (ALS) is an incurable, neurological disease characterized by a progressive degeneration of the motor nervous system. The symptoms of the disease are progressive muscle weakness that eventually causes paralysis and respiratory failure. The survival time from the onset of the disease is two to five years. There is currently no cure for ALS and treatment consists of symptomatic relief. The aim of the study was to illuminate quality of life and well-being in patients with the incurable disease ALS. The method used was a literature review based on thirteen scientific articles that were analyzed and compiled. The results revealed four themes; the importance of physical deterioration and loss of bodily function, the importance of support from family, friends and caregivers, the importance of living in the present and ignore the future and the importance of feeling hope and maintain a positive outlook on life. It is significant that more qualitative studies are being made, studies that explore patients' individual experiences of living with the disease ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that leads to respiratory compromise and eventually death within two to five years. Even though people with ALS must make many treatment decisions, none has such a significant impact on quality of life and survival as the one pertaining to assisted ventilation. A qualitative research study was undertaken to elicit factors that are pertinent to this decision-making process. Ten individual, semi-structured interviews were conducted with individuals with ALS. Six main themes emerged from the interviews. These are: meaning of the intervention, the importance of context, values, and fears in decision-making, the need for information, and adaptation/acceptance of the intervention. Based on these findings, it is argued that a pluralistic conception of autonomy as well as a shared decision-making model is better suited to give high priority to patient autonomy in this context. Some recommendations to improve clinical practice are proposed.

Purpose: The purpose of this project was to look at the costs of individuals with Alzheimer’s disease and related dementias (ADRD), ALS, and MS in long stay home care in Ontario, Canada. The specific goals were to produce estimates of costs for these individuals, as well as identify clinical and personal characteristics associated with these costs. This project also tested the effectiveness of the Resource Utilization Group for home care case-mix system for use in these special populations. Methods: This project was conducted using a secondary analysis of assessment data from the Canadian Staff Time Resource Intensity Verification Project, a 13-week study of home care costs (N=435 141). The project was guided by the Andersen and Newman (1973) framework for healthcare resource utilization. Descriptive characteristics and mean costs were produced using bivariate frequency and means procedures for each of three conditions. Predictors of costs were identified for each of the three neurological conditions through multivariate regression analysis conducted separately for each condition. In total 41 independent variables were included into the bivariate and multivariate analyses. The dependent variable was the total weekly formal and informal home care costs across all multivariate analyses. Results: In total, ADRD, ALS, or MS diagnoses were present in 16% of the assessments. The mean costs for the three conditions combined were $594.81. The mean costs for ADRD, ALS, and MS were $593.32, $898.41, and $574.92, respectively. Characteristics that were predictive of cost across all conditions included the Resource Utilization Group for home care case-mix system, ADL functionality, IADL functionality, cognitive performance, unsteady gait, stair use, difficulty swallowing, respiratory challenges, and bowel incontinence. The Resource Utilization Group for home care case-mix system had the highest level of explained variance of any single item tested in this project across all conditions. However, other clinical characteristics also contributed substantial levels of explained variance to the models for each of the three conditions. Conclusions: The findings from this project suggest that although diagnosis of ADRD, ALS, and/or MS can describe cost, clinical characteristics are the most important predictors of costs for individuals with these conditions. In addition, the Resource Utilization Group for home care case-mix system can adequately predict costs of individuals with these conditions. The addition of some clinical characteristics would likely improve the predictive abilities of the Resource Utilization Group for home care case-mix system.