Alaraajojen lihasten spastisuus ennen ja jälkeen avustetun polkuharjoittelun

Opinnäytetyön tavoitteena oli kerätä tietoa aivoverenkiertohäiriötä, selkäydinvauriota sekä CP-vammaa sairastavien neurologisten asiakkaiden spastisten alaraajojen lihasten spastisuuden aiheuttaman lihasaktivaation mahdollisesta muutoksesta ennen ja jälkeen avustetulla polkulaitteella suoritetun polkuharjoituksen. Tarkoituksena oli tuottaa tutkittua tietoa kyseisen terapiamuodon vaikutuksesta edellä mainittuja oireyhtymiä sairastavien kuntoutuksessa. Toimeksiantaja voi hyödyntää tuloksia suunnitellessaan ja arvioidessaan neurologisten asiakkaiden kuntoutuksessa käytettäviä terapiamuotoja. Lisäksi tarkoituksena oli tuottaa fysioterapia-alalle tietoa terapiamuodon vaikutuksesta alaraajojen spastisuuteen. Työn tekijät syvensivät työn kautta omaa ammattitaitoaan tulevaa ammattia varten. Opinnäytetyömme tutkimusongelmana oli miten polkulaitteella suoritettu 20 minuutin avustettu polkuliike vaikuttaa aivoverenkiertohäiriötä, selkäydinvauriota sekä CP-vammaa sairastavien neurologisten asiakkaiden spastisuuden aiheuttamaan alaraajojen lihasaktivaatioon. Opinnäytetyö toteutettiin tapaustutkimuksena, johon osallistui viisi tutkimushenkilöä. Tutkimuksen aineisto kerättiin määrällisin menetelmin, joita olivat elektromyografia (EMG), Modified Modified Ashworth Scale (MMAS) sekä kysymyslomake. EMG ja MMAS mittaukset suoritettiin yhtäaikaisesta ennen polkuharjoitusta ja sen jälkeen. Mittareilla saadut tulokset analysoitiin MegaWin-ohjelmalla ja Microsoft Excel-taulukkolaskentaohjelmalla. Tulokset on esitetty numeerisessa ja graafisessa muodossa. Tutkimuksesta saatujen tulosten mukaan spastisuuden aiheuttama lihasaktivaatio väheni polkuharjoittelun jälkeen jokaisessa mitatussa lihaksessa EMG- ja MMAS -mittareilla mitattuna. Myös kysymyslomakkeella saatujen tulosten mukaan polkuharjoittelun vaikutukset spastisuuteen ovat positiivisia. Näin ollen tutkimustulosten perusteella avustetulla polkuharjoittelulla oli lihasten spastisuutta alentava vaikutus. Pienen tutkimusjoukon johdosta tuloksia ei voi kuitenkaan yleistää, mutta ne ovat suuntaa-antavia.The aim of this thesis is to gather information on possible changes in the spasticity of the lower limb muscles before and after assisted cycling exercise in clients with stroke, spinal cord injury and cerebral palsy. The purpose of this thesis is to produce information about the effects of the assisted cycling exercise in rehabilitation with clients suffering from the above mentioned injuries. The commissioner, Kemijärven Fysikaalinen Hoitolaitos Ky, can benefit from the achieved results while planning the rehabilitation of neurological clients. The authors’ purpose is to generate knowledge on the effects of assisted cycling exercise in spasticity of the lower limb muscles for physiotherapy field to use. The authors benefit from the thesis by obtaining their own expertise for the upcoming profession. The research problem of this thesis was to discover how the 20-minute assisted cycling exercise affects the spasticity of the lower limbs muscles in clients with stroke, spinal cord injury and cerebral palsy. This thesis is a case study in which participated five study subjects. The research data was gathered with the following quantitative methods: Electromyography (EMG), Modified Modified Ashworth Scale (MMAS) and questionnaire. EMG and MMAS were administrated simultaneously before and after assisted cycling exercise. The results were analysed with MegaWin-program and Microsoft Excel Spreadsheet. The results are displayed in numerical and graphical form. The results of this thesis show that after the assisted cycling exercise the muscle activation caused by spasticity, previously measured by EMG and MMAS, was reduced in every tested muscle. According to results from the questionnaire the effects of assisted cycling exercise was also positive. Therefore, it could be said that assisted cycling exercise reduces the spasticity in lower limb muscles. Due to the limited amount of participant in the study group, the results cannot be generalised, nevertheless, they can be used as directional information

Pharmacoepidemiology and Drug Safety's special issue on validation studies

Administrative claims and other routinely collected data provide the foundation for many drug utilization, safety, and effectiveness studies. These databases provide a rich source of timely health care information on large, well‐defined populations. Yet information contained in these databases is generally captured using standardized systems, summarizing complex medical histories, clinical diagnoses, and services and therapies provided to patients. Thus, carefully designed validation studies that evaluate the accuracy of coded algorithms to identify health‐related exposures, outcomes, and covariates against a reference standard are an essential component for demonstrating the validity of their use for research purposes

Dynamical supersymmetry breaking and unification of couplings

We consider the possibility of unification of the Supersymmetric Standard Model gauge groups with those of the dynamical supersymmetry breaking (DSB) sector in theories with gauge mediated supersymmetry breaking. We find constraints on the DSB gauge group beta function that come from unification of the gauge coupling constants of the two sectors. These constraints are satisfied by a fairly wide class of models. We discuss possible unification scenarios in the context of a simple model.Comment: 7 pages, LaTeX; grant numbers correcte

Oncology pharmacist-led medication reconciliation among cancer patients initiating chemotherapy

Background: Pharmacist-led medication reconciliation (PMR) ensures adequate recording and use of medications by patients. PMR may be important for cancer patients initiating new therapies, as they have a high burden of medication use and are more susceptible to inadvertent medication discrepancies. To describe medication changes (additions, discontinuations, and modifications) made to the electronic health record during a PMR among cancer patients initiating chemotherapy. Methods: From October 2011 to March 2012, 397 cancer patients initiating chemotherapy underwent a PMR at the University of North Carolina Cancer Hospital. Self-reported medications and those in the patients’ electronic health record were reviewed. Log-binomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals for the associations between patient characteristics and medication changes made to the electronic health record. Results: Mean age at time of the PMR was 58. Median number of medications taken prior to the PMR was 10 and median time to PMR completion was 11 min. Vitamins and herbal supplements accounted for the largest proportion of medication additions (38%) and modifications (20%). Antimicrobials accounted for the largest share of discontinuations (15%). After adjustment for all other covariates, patients aged 60–69 years were more likely to have additions than those aged 50 and under (aPR = 1.47, 95%CI: 1.10–1.97). Patients 70 years and over were more likely to have modifications (aPR = 1.74, 95%CI: 1.07–2.82). Conclusion: Our results show that most cancer patients had a medication change in the electronic health record. A brief oncology PMR can accurately capture and improve medication safety by preventing prescribing and administration errors

Patterns of first-line targeted therapy utilization and adherence among older adults diagnosed with metastatic renal cell carcinoma

Background: Despite the rapid approval of targeted therapies for metastatic renal cell carcinoma (mRCC) evidence on real world treatment patterns remains limited. This study evaluated patterns of first-line targeted therapy utilization and adherence in older adults, a population with a high burden of RCC. Methods: 2093 patients aged ≥66 years with a primary diagnosis of mRCC were identified from United States (US)-based cancer registry and administrative claims data (2007–2015). We included only patients with de novo disease. We assessed the initiation of first-line targeted therapy within four months of diagnosis and persistence and adherence to targeted therapy, using the proportion of days covered (PDC). Multivariable logistic regression yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to describe characteristics associated with targeted therapy versus no targeted therapy initiation and for high (≥80% PDC) versus low adherence. Results: 28.8% of patients received first-line targeted therapy within four months of diagnosis, with the proportion of patients receiving targeted therapy increasing over time. Older age (one-year increment OR:0.95 95%CI 0.93, 0.97), high comorbidity burden (OR:0.65 95%CI0.46, 0.93) and clear cell histology (OR:1.54 95%CI 1.19, 2.00) were associated with targeted therapy initiation. 48.2% of patients exhibited a high PDC to oral targeted therapy at 120 days, which was attenuated with inclusion of patients who died during the time period (34.2% PDC ≥80%). Conclusion: Increasing age, high comorbidity burden and non-clear cell histology were associated with decreased targeted therapy initiation among patients with de novo mRCC. Our findings suggest adherence to oral therapies was low; future research exploring the mechanisms and impact of low adherence in this older patient population is warranted

Decreased antihyperglycemic drug use driven by high out-of-pocket costs despite medicare coverage gap closure

OBJECTIVE Using the 2016 Medicare Part D coverage gap as an example, we explored effects of increased out-of-pocket costs on adherence to branded dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients without financial subsidies relative to subsidized patients who do not experience increased spending during the gap. We also explored seasonality of reinitiation, because discontinuers may be more likely to reinitiate in January when benefits reset. RESEARCH DESIGN AND METHODS We identified DPP-4i or sulfonylurea initiators, aged ‡66 years, from a 20% sample of 2015–2016 Medicare claims. Difference-in-differences Poisson regression was used to compare adherence before and after entering the coverage gap between nonsubsidizedand subsidized patients.Among discontinuers, monthly hazardratios (HRs) for reinitiation relative to January 2016 were derived with Cox models. As a second control, we repeated analyses using sulfonylureas, generic low-cost alternatives. RESULTS In 2016, 8,096 subsidized and 6,173 nonsubsidized DPP-4i initiators entered the coverage gap. For nonsubsidized patients, copayment in the coverage gap was 45% ($227 per DPP-4i prescription), and adherence decreased from 68.4% to 49.0% after gap entry. Accounting for adherence differences in subsidized patients, nonsubsidized patients demonstrated reduced adherence to DPP-4i (differencein-difference: 216.9%; 95% CI 218.7%, 215.1%) but not sulfonylureas (21.6%; 95% CI 23.4%, 0.2%). Reinitiation was lowest in the months before January (HR 0.4–0.5) among nonsubsidized DPP-4i patients, demonstrating a strong seasonal pattern. CONCLUSIONS Increased out-of-pocket costs negatively affect adherence and reinitiation of branded antihyperglycemic drugs among patients without financial subsidies. Despite closure of the coverage gap, affordability remains a concern given increasing list prices for many drugs on Medicare and the growing use of deductibles and coinsurance by commercial health plans

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis : From the PARADIGM Registry

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume 651.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP

Channel-Coupling Effects in High-Energy Hadron Collisions

The Two-Gluon Model of the Pomeron predicts strongly size-dependent high-energy hadron cross sections. Yet experimental cross sections for radially excited mesons appear surprisingly close in value. The strong coupling of these mesons in hadron collisions also predicted by the model permits a qualitative understanding of this puzzling behavior in terms of eigenmode propagation with a common eigen-$\sigma$. A detailed semiempirical coupled-channel model of the Pomeron is constructed to elucidate this and other features of high-energy hadron cross sections.Comment: 13 pages, latex, no figure

Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension

Background: Bone morphogenetic protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP receptor type 2 (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH. Methods: We used a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between vascular endothelial growth factor receptor 3 (VEGFR3) and BMPR2. Additional in vitro studies were performed by using human endothelial cells, including primary lung endothelial cells from subjects with PAH. Results: Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. Endothelial cells with disrupted VEGFR3 expression failed to respond to exogenous BMP stimulation. Mechanistically, VEGFR3 is physically associated with BMPR2 and facilitates ligand-induced endocytosis of BMPR2 to promote phosphorylation of SMADs and transcription of ID genes. Conditional, endothelial-specific deletion of Vegfr3 in mice resulted in impaired BMP signaling responses, and significantly worsened hypoxia-induced pulmonary hypertension. Consistent with these data, we found significant decrease in VEGFR3 expression in pulmonary arterial endothelial cells from human PAH subjects, and reconstitution of VEGFR3 expression in PAH pulmonary arterial endothelial cells restored BMP signaling responses. Conclusions: Our findings identify VEGFR3 as a key regulator of endothelial BMPR2 signaling and a potential determinant of PAH penetrance in humans