Saskatchewan Health Authority

PURPOSE: To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen (ER) and progesterone receptor (PgR) testing in breast cancer guideline. METHODS: A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. RECOMMENDATIONS: The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines.

BACKGROUND: Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism. METHODS: Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia. RESULTS: The variant was not observed in public databases or identified in unrelated subjects. CONCLUSIONS: The substitution's evolutionary conservation and protein modeling provide additional support for pathogenicity as the amino acid perturbs the same amphipathic alpha helical structure as the previously described pathogenic mutations.

Stroke rehabilitation is a progressive, dynamic, goal-orientated process aimed at enabling a person with impairment to reach their optimal physical, cognitive, emotional, communicative, social and/or functional activity level. After a stroke, patients often continue to require rehabilitation for persistent deficits related to spasticity, upper and lower extremity dysfunction, shoulder and central pain, mobility/gait, dysphagia, vision, and communication. Each year in Canada 62,000 people experience a stroke. Among stroke survivors, over 6500 individuals access in-patient stroke rehabilitation and stay a median of 30 days (inter-quartile range 19 to 45 days). The 2015 update of the Canadian Stroke Best Practice Recommendations: Stroke Rehabilitation Practice Guidelines is a comprehensive summary of current evidence-based recommendations for all members of multidisciplinary teams working in a range of settings, who provide care to patients following stroke. These recommendations have been developed to address both the organization of stroke rehabilitation within a system of care (i.e., Initial Rehabilitation Assessment; Stroke Rehabilitation Units; Stroke Rehabilitation Teams; Delivery; Outpatient and Community-Based Rehabilitation), and specific interventions and management in stroke recovery and direct clinical care (i.e., Upper Extremity Dysfunction; Lower Extremity Dysfunction; Dysphagia and Malnutrition; Visual-Perceptual Deficits; Central Pain; Communication; Life Roles). In addition, stroke happens at any age, and therefore a new section has been added to the 2015 update to highlight components of stroke rehabilitation for children who have experienced a stroke, either prenatally, as a newborn, or during childhood. All recommendations have been assigned a level of evidence which reflects the strength and quality of current research evidence available to support the recommendation. The updated Rehabilitation Clinical Practice Guidelines feature several additions that reflect new research areas and stronger evidence for already existing recommendations. It is anticipated that these guidelines will provide direction and standardization for patients, families/caregiver(s), and clinicians within Canada and internationally.

Background & aimsThe incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century.MethodsWe systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn’s disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD.ResultsA total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous.ConclusionsRates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries. The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century. We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn’s disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD. A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous. Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

OBJECTIVE: The failure of offenders to complete psychological treatment can pose significant concerns, including increased risk for recidivism. Although a large literature identifying predictors of offender treatment attrition has accumulated, there has yet to be a comprehensive quantitative review. METHOD: A meta-analysis of the offender treatment literature was conducted to identify predictors of offender treatment attrition and examine its relationship to recidivism. The review covered 114 studies representing 41,438 offenders. Sex offender and domestic violence programs were also examined separately given their large independent literatures. RESULTS: The overall attrition rate was 27.1% across all programs (k = 96), 27.6% from sex offender programs (k = 34), and 37.8% from domestic violence programs (k = 35). Rates increased when preprogram attrition was considered. Significant predictors included demographic characteristics (e.g., age, rw = -.10), criminal history and personality variables (e.g., prior offenses, rw = .14; antisocial personality, rw = .14), psychological concerns (e.g., intelligence, rw = -.14), risk assessment measures (e.g., Statistical Information on Recidivism scale, rw =.18), and treatment-related attitudes and behaviors (e.g., motivation, rw = -.13). Results indicated that treatment noncompleters were higher risk offenders and attrition from all programs significantly predicted several recidivism outcomes ranging from rw = .08 to .23. CONCLUSIONS: The clients who stand to benefit the most from treatment (i.e., high-risk, high-needs) are the least likely to complete it. Offender treatment attrition can be managed and clients can be retained through an awareness of, and attention to, key predictors of attrition and adherence to responsivity considerations.

Interest in serotonergic involvement in Parkinson's disease (PD) has focussed recently on the possibility that the remaining serotonin neurons innervating striatum (caudate and putamen) might release dopamine as a 'false transmitter'--an action that could have both beneficial and harmful (e.g. promotion of levodopa-induced dyskinesias) consequences. Evidence for a brain serotonergic disturbance in PD is derived in large part from findings of decreased binding of different radioligands to the serotonin transporter (SERT), one 'marker' of serotonin neurons. However, it is not known whether the reported changes in SERT binding reflect actual changes in levels of SERT protein or whether concentrations of all serotonin markers are similarly and markedly decreased in the two striatal subdivisions. We measured levels of SERT immunoreactivity, and for comparison, protein levels of tryptophan hydroxylase (TPH; the marker synthetic enzyme) using a Western blot procedure, as well as concentrations of serotonin, its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and dopamine by HPLC in post-mortem striatum of patients with PD and normal controls. Whereas concentrations of dopamine were severely decreased (caudate, -80%; putamen, -98%) and showed little (caudate) or no (putamen) overlap between individual control and patient values, levels of all four serotonin markers were less markedly reduced (-30% to -66%) with some patients having distinctly normal levels. Unlike the preferential loss of dopamine in putamen, the caudate was affected more than putamen by loss of all serotonin markers: serotonin (-66% versus -51%), 5-HIAA (-42% versus -31%), SERT (-56% versus -30%) and TPH (-59% versus -32%). Striatal serotonin concentration was similar in the subset of patients reported to have had dyskinesias versus those not reported to have had this drug complication. Previous findings of decreased SERT binding are likely explained by loss of SERT protein. Reduced striatal levels of all of the key serotonergic markers (neurotransmitter and metabolite, transporter protein, synthesizing enzyme protein) provide strong evidence for a serotonergic disturbance in PD, but with some patients affected much more than others. The more marked caudate reduction suggests that raphe neurons innervating this area are more susceptible to 'damage' than those innervating putamen and that any functional impairment caused by striatal serotonin loss might primarily involve the caudate. Questions related to the, as yet undetermined, clinical consequences in PD of a striatal serotonin deficiency (caudate: cognitive impairment?) and preservation (putamen: levodopa-induced dyskinesias?) should be addressed in prospective brain imaging and pharmacological studies.

Respiratory tract disease can be associated with primary or secondary bacterial infections in dogs and cats and is a common reason for use and potential misuse, improper use, and overuse of antimicrobials. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, the International Society for Companion Animal Infectious Diseases convened a Working Group of clinical microbiologists, pharmacologists, and internists to share experiences, examine scientific data, review clinical trials, and develop these guidelines to assist veterinarians in making antimicrobial treatment choices for use in the management of bacterial respiratory diseases in dogs and cats.

PURPOSE.—: To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. METHODS.—: A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. RECOMMENDATIONS.—: The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .

The current investigation is a meta-analysis of the predictive accuracy of three well-known forensic instruments used to appraise risk with young offenders: youth adaptations of the Level of Service Inventory and Psychopathy Checklist and the Structured Assessment of Violence Risk for Youth. Through several avenues, 49 potentially suitable published and unpublished studies (across 44 samples representing 8,746 youth) were identified and evaluated for inclusion. Predictive accuracy for general, nonviolent, violent, and sexual recidivism was examined for the three sets of measures. Mean weighted correlations for each of the three measures were significant in the prediction of general, nonviolent, and violent recidivism, with no single instrument demonstrating superior prediction. Separate analyses of specific young offender groups further supported the predictive accuracy of youth adaptations of the Level of Service Inventory among male, female, Aboriginal, and non-Aboriginal youth. Implications regarding the utility of young offender risk measures for enhancing clinical service provision with youth clientele are discussed.

BACKGROUND: Immigrants from culturally, ethnically, and linguistically diverse countries face many challenges during the resettlement phase, which influence their access to healthcare services and health outcomes. The "Healthy Immigrant Effect" or the health advantage that immigrants arrive with is observed to deteriorate with increased length of stay in the host country. METHODS: An exploratory qualitative design, following a community-based research approach, was employed. The research team consisted of health researchers, clinicians, and community members. The objective was to explore the barriers to healthcare access among immigrants with limited English language proficiency. Three focus groups were carried out with 29 women and nine men attending English language classes at a settlement agency in a mid-sized city. Additionally, 17 individual interviews were carried out with healthcare providers and administrative staff caring for immigrants and refugees. RESULTS: A thematic analysis was carried out with transcribed focus groups and healthcare provider interview data. Both the healthcare providers and immigrants indicated that limited language proficiency often delayed access to available healthcare services and interfered with the development of a therapeutic relationship between the client and the healthcare provider. Language barriers also impeded effective communication between healthcare providers and clients, leading to suboptimal care and dissatisfaction with the care received. Language barriers interfered with treatment adherence and the use of preventative and screening services, further delaying access to timely care, causing poor chronic disease management, and ultimately resulting in poor health outcomes. Involving untrained interpreters, family members, or others from the ethnic community was problematic due to misinterpretation and confidentiality issues. CONCLUSIONS: The study emphasises the need to provide language assistance during medical consultations to address language barriers among immigrants. The development of guidelines for recruitment, training, and effective engagement of language interpreters during medical consultation is recommended to ensure high quality, equitable and client-centered care.

A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case-control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch-German-Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.

I read the interesting report by Olanow et al.1 regarding factors predictive of the development of levodopa (l-dopa)-induced dyskinesia and wearing-off in Parkinson's disease. l-Dopa has been widely used for more than 40 years, but a dose-finding study was never performed. I congratulate the authors for addressing this very important issue of l-dopa dosing. Their study provides scientific rationale for using as low a dose of l-dopa as clinically necessary for symptomatic control of Parkinson's disease while reducing dyskinesias and motor response fluctuations. Although intravenous l-dopa was reported as effective in 1961,2 oral therapy with this drug became possible only after a 1967 report by Cotzias et al.3 based on a study of 17 patients. They used dihydroxyphenylalanine, DL-3,4-(alanine-1-14C) (D-l-dopa), "…because of the great expense of the l-compound."3 The dose of D-l-dopa in most of their patients was 9 g or higher and was up to 16 g in some patients.3 Soon, l-dopa became commercially available, but there was no clinical trial to establish the optimal dose. Neurologists used the l-dopa dose with which they felt comfortable. Dyskinesia was the first motor complication of l-dopa observed by most experts.4 On 6 g of l-dopa daily (equivalent to 1200 mg carbidopa–l-dopa [Sinemet; Merck & Company, Inc., Whitehouse Station, NJ]), 58% of patients had dyskinesias by the end of 6 months, and 75% had dyskinesias by the end of 1 year.4 We received authorization for l-dopa use as the second wave of neurologists in this field. As such, we had access to some of the observations made by others, and we witnessed severe dyskinesia in some patients on high l-dopa doses. The benefit/adverse effects profile did not seem to be favorable for l-dopa therapy. Therefore, we decided to use a lower dose and slower titration of l-dopa, targeting a dose of 3 g (Sinemet 600 mg) or lower. We reported our 12-year observations on low-dose l-dopa therapy in 1984.5 The incidence of dyskinesia was markedly lower than reported by others.4 By the end of 1 year, only 15% of our patients had dyskinesia, and only 3% had wearing-off or wearing-on/wearing-off.5 We have continued to use a low dose of l-dopa. The incidence of both dyskinesias and motor response fluctuations in our longitudinally followed autopsy cases of Parkinson's disease was much lower compared with the incidence reported in most of the literature.6 It is encouraging to see that an l-dopa dosing regimen similar to that started empirically in the late 1960s now has more robust data to support it. Ali H. Rajput, MBBS, FRCPC University of Saskatchewan/Saskatoon Health Region, Saskatoon, Saskatchewan, Canada The author made no disclosures.

Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD), and its severity and magnitude increases as the disease progresses, leading to significant disability and a negative effect on quality of life. Refractory dyspnea is a common and difficult symptom to treat in patients with advanced COPD. There are many questions concerning optimal management and, specifically, whether various therapies are effective in this setting. The present document was compiled to address these important clinical issues using an evidence-based systematic review process led by a representative interprofessional panel of experts. The evidence supports the benefits of oral opioids, neuromuscular electrical stimulation, chest wall vibration, walking aids and pursed-lip breathing in the management of dyspnea in the individual patient with advanced COPD. Oxygen is recommended for COPD patients with resting hypoxemia, but its use for the targeted management of dyspnea in this setting should be reserved for patients who receive symptomatic benefit. There is insufficient evidence to support the routine use of anxiolytic medications, nebulized opioids, acupuncture, acupressure, distractive auditory stimuli (music), relaxation, handheld fans, counselling programs or psychotherapy. There is also no evidence to support the use of supplemental oxygen to reduce dyspnea in nonhypoxemic patients with advanced COPD. Recognizing the current unfamiliarity with prescribing and dosing of opioid therapy in this setting, a potential approach for their use is illustrated. The role of opioid and other effective therapies in the comprehensive management of refractory dyspnea in patients with advanced COPD is discussed.

BACKGROUND: Individual variations in the course of Lewy body Parkinson disease (PD) are well known. Patients have been classified into different clinical subtypes to identify differences in the course among the subgroups. Several studies indicate that the outcome is more favorable in tremor dominant (TD) cases but others report no difference. A majority of progression studies are based on cross-sectional single point data or short-term clinical observations. The lack of longitudinally followed autopsy-confirmed PD cohort remains a major weakness in the literature. Biochemical studies of brain indicate most pronounced abnormalities in akinetic/rigid (AR) and the least in TD cases. We postulate that PD course in these subtypes is concordant with the biochemical findings. OBJECTIVE: To compare the course in TD, mixed (MX), and AR subtypes of PD. METHODS: Longitudinal clinical follow-up and autopsy studies were performed on 166 patients with PD over 39 years (1968-2006). Patients were classified into TD, AR, and MX based on the entire clinical course. Only the pathologically confirmed PD cases were included. RESULTS: Sixty-six percent of cases had MX, 26% AR, and 8% TD profile. The age at onset was younger (p < 0.001) and progression to Hoehn & Yahr stage 4 was slower (p = 0.016) in the TD cases. Dementia was most common in AR (p = 0.039) and the least common in TD. In general, the course was most favorable in TD, followed by MX and AR subgroups. CONCLUSION: The three subtypes of Parkinson disease have different courses which are concordant with the differences in brain biochemical abnormalities.

In the early months of the COVID-19 pandemic with no designated cure or vaccine, the only way to break the infection chain is self-isolation and maintaining the physical distancing. In this article, we present a potential application of the Internet of Things (IoT) in healthcare and physical distance monitoring for pandemic situations. The proposed framework consists of three parts: a lightweight and low-cost IoT node, a smartphone application (app), and fog-based Machine Learning (ML) tools for data analysis and diagnosis. The IoT node tracks health parameters, including body temperature, cough rate, respiratory rate, and blood oxygen saturation, then updates the smartphone app to display the user health conditions. The app notifies the user to maintain a physical distance of 2 m (or 6 ft), which is a key factor in controlling virus spread. In addition, a Fuzzy Mamdani system (running at the fog server) considers the environmental risk and user health conditions to predict the risk of spreading infection in real time. The environmental risk conveys from the virtual zone concept and provides updated information for different places. Two scenarios are considered for the communication between the IoT node and fog server, 4G/5G/WiFi, or LoRa, which can be selected based on environmental constraints. The required energy usage and bandwidth (BW) are compared for various event scenarios. The COVID-SAFE framework can assist in minimizing the coronavirus exposure risk.

PURPOSE: To examine relationships between selected sociodemographic, health-related and environmental factors and levels of physical activity in older adults across three age groups. METHODS: Seven hundred sixty-four older adults (mean age = 77.4 +/- 8.6 yr) from a midsize Canadian city completed a self-administered questionnaire under researcher supervision. Level of physical activity was determined using the Physical Activity Scale for the Elderly (PASE). Correlates of physical activity were examined using previously validated questionnaires. The findings pertaining to personal and environmental factors are presented. RESULTS: Overall, significantly higher mean PASE scores were seen in those individuals in the following categories: male (P < 0.001), married or common-law (P < 0.001), not living alone (P < 0.001), not living in senior's housing (P < 0.001), higher levels of education (P < 0.001) and higher incomes (P < 0.001). Better physical health showed significant positive associations (P < 0.001) with PASE score. Individuals reporting at least four or more chronic health conditions had significantly lower PASE scores than those reporting no chronic conditions (P < 0.001). Significantly lower PASE scores were also reported in those using domestic services (P < 0.001). Higher PASE scores were related to the presence of hills, biking and walking trails, street lights, various recreation facilities, seeing others active and unattended dogs (P < 0.001 to P < 0.05). CONCLUSION: An understanding of the factors that influence physical activity behavior in older adults is critical to developing effective intervention strategies that will address the problem of physical inactivity in this population, and in doing so, improve the health status and quality of life of the older adult, while having a significant impact on healthcare expenditures.

BACKGROUND AND PURPOSE: The purposes of this study were: (1) to assess the effectiveness of a 16-week progressive program of home-based, videotape-based, low-impact aerobic exercise on physical function and signs and symptoms of fibromyalgia in previously sedentary women aged 20 to 55 years and (2) to compare the effects of 1 long exercise bout versus 2 short exercise bouts per training day (fractionation) on physical function, signs and symptoms of fibromyalgia, and exercise adherence. SUBJECTS: One hundred forty-three sedentary women were randomly assigned to 1 of 3 groups: a group who trained using a long bout of exercise (LBE group, n=51), a group who trained using short bouts of exercise (SBE group, n=56), and a group who performed no exercise (NE group, n=36). METHODS: The SBE group exercised twice daily, and the LBE group worked out once daily. Both groups progressed in total daily training duration from 10 to 30 minutes, 3 to 5 times a week, for 16 weeks. Physical and psychological well-being, symptoms, and self-efficacy were evaluated using a multivariate analysis of variance. RESULTS: Dropout rates for the NE, SBE, and LBE groups were 14%, 38%, and 29%, respectively. The NE group differed from the LBE group in disease severity, self-efficacy, and psychological well-being (midtest, efficacy analysis) and from the SBE group in disease severity and self-efficacy (posttest, efficacy analysis). Exercise adherence was greater for the LBE group than for the SBE group between weeks 5 and 8 of the training program. No other differences between exercise groups were found. DISCUSSION AND CONCLUSION: Progressive, home-based, low-impact aerobics improved physical function and fibromyalgia symptoms minimally in participants who completed at least two thirds of the recommended exercise. Fractionation of exercise training provided no advantage in terms of exercise adherence, improvements in fibromyalgia symptoms or physical function. High attrition rates and problems with exercise adherence were experienced in both exercise groups.

BACKGROUND: Patients with Parkinson disease (PD) may be akinetic/rigid, be tremor dominant, or have comparable severity of these motor symptoms (classic). The pathophysiologic basis of different PD phenotypes is unknown. This study assessed pallidal and striatal dopamine level patterns in different motor subgroups of PD and normal control brains. METHODS: Globus pallidus and striatum dopamine (DA) levels were measured with high performance liquid chromatography in eight autopsy confirmed PD and five control frozen brains. RESULTS: DA levels in the external globus pallidus (GPe) of normal brains were nearly six times greater than in the internal pallidum (GPi). In PD, the mean loss of DA was marked (-82%) in GPe and moderate (-51%) in GPi. DA loss of variable degree was seen in different subdivisions of GPe and GPi in PD; however, DA levels were near normal in the ventral (rostral and caudal) GPi of PD cases with prominent tremor. There was marked loss of DA (-89%) in the caudate and severe loss (-98.4%) in the putamen in PD. The pattern of pallidal DA loss did not match the putaminal DA loss. CONCLUSION: There is sufficient loss of dopamine (DA) in external globus pallidus and the internal globus pallidum (GPi) as may contribute to the motor manifestations of Parkinson disease (PD). The possible functional disequilibrium between GABAergic and DAergic influences in favor of DA in the caudoventral parts of the GPi may contribute to resting tremor in tremor dominant and classic PD cases.

BACKGROUND: Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions. METHODS: Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates. RESULTS: For hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions. CONCLUSIONS: The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.

OBJECTIVE: To correlate autopsy findings with the clinical course and disability profile in clinically diagnosed longitudinally followed autopsied essential tremor (ET) patients. METHODS: All ET patients followed by one neurologist between 1970 and 2001 who came to autopsy were included. Clinical features and disability were recorded prospectively. Autopsy studies were performed by a qualified neuropathologist. RESULTS: Twenty cases (10 men and 10 women) had ET onset between childhood and age 68 (median 46.5 years). Six cases had additional features of Parkinson syndrome (PS), with presence of bradykinesia, rigidity, and rest tremor (RT). These included progressive supranuclear palsy (PSP; n = 2), drug-induced parkinsonism (n = 2), idiopathic Parkinson disease (PD; n = 1), and basal ganglia status cribrosus (n = 1). Of the remaining 14 ET cases, 6 had additional RT but no bradykinesia or rigidity. Ten of these 14 (71%) reported physical disability. Eleven of the 14 (79%) had only upper limb (UL) tremor at onset, and 8 of these 11 (73%) had subsequent cranial extension of tremor. Two patients clinically had mild cerebellar ataxia but no cerebellar histologic abnormality. There was no consistent brain pathology in the ET or ET + RT cases. CONCLUSIONS: UL tremor was the most common onset, which often progressed to the cranial musculature. Functional disability and psychological distress were common in these patients. Functional disability was related to the UL tremor. Six of 20 (30%) had additional features of PS. Six of the remaining 14 (43%) had ET and RT; there was no identifiable pathology in these cases. The risk of PD in ET cases was comparable with that in the general population. PSP in two cases was incidental comorbidity.