A single centre prospective study of three device-assisted therapies for Parkinson's disease.

Comparative studies assessing outcomes with the three device-assisted therapies could help to individualise treatment for patients living with Parkinson's disease. We designed a single-centre non-randomised prospective observational study assessing the quality of life (QoL), motor and non-motor outcomes at 6 and 12-months in patients treated with subcutaneous apomorphine continuous 16-hours infusion (APO), levodopa-carbidopa intestinal gel (LCIG) or subthalamic nucleus deep brain stimulation (STN-DBS). In this study, 66 patients were included (13 APO; 19 LCIG; 34 STN-DBS). At baseline, cognitive, non-motor and motor scores were significantly less severe in the STN-DBS group, whereas the LCIG group had a longer disease duration and higher non-motor scores. In the APO group, there were no statistically significant changes in non-motor, motor and QoL scales. The LCIG group had significant changes in QoL and motor scales that were significant after multiple comparison analysis at 6 and 12-months. The STN-DBS group showed improvement in QoL scores and non-motor and motor scores at 6 and 12-months after multiple comparison analysis. In this real-life prospective study, device-assisted therapies showed differences in their effects on QoL and motor and non-motor function at 12-months. However, there were also differences in baseline characteristics of the patient groups that were not based on pre-determined selection criteria. Differences in characteristics of patients offered and/or treatment with different device-assisted therapies may reflect within-centre biases that may, in turn, influence perceptions of treatment efficacy or outcomes. Treatment centres should be aware of this potential confounder when assessing and offering device-assisted treatment options to their patients and potential baseline differences need to be taken into consideration when comparing the results of non-randomised studies.

Challenges in managing late-stage Parkinson's disease: Practical approaches and pitfalls.

BACKGROUND: Parkinson's disease is a universally progressive neurodegenerative disease. People living with Parkinson's disease for many years face progression from early- to mid- to late-stage Parkinson's disease (LSPD). While levodopa-responsive, predominantly motor features constitute the majority of symptom burden in early-stage Parkinson's disease, the disability in LSPD is characterised mainly by non-motor symptoms, which may be poorly levodopa responsive. OBJECTIVE: The aim of this article is to discuss recognition of LSPD and suggest strategies that may assist patients with LSPD in the community. DISCUSSION: The milestones of frequent falls, cognitive dysfunction, hallucinations and the need for residential care signal LSPD and predict time to death. Treatment aims shift to focus on patient comfort and conscientious prevention of exacerbations. In this article, challenges such as autonomic dysregulation, pain, cognitive decline and psychosis are addressed. These authors advocate a holistic approach, including supporting not only the patient with LSPD but also their carers.

An approach to acute clinical deterioration in patients with late-stage Parkinson's disease.

BACKGROUND: Idiopathic Parkinson's disease is a slowly progressive neurodegenerative disease. In the absence of disease-modifying therapies, patients inevitably progress to late-stage disease, characterised by a shift towards increasing disability from predominantly non-motor symptoms, which may be poorly levodopa responsive. OBJECTIVE: The aim of this article is to provide general practitioners (GPs) with a practical approach to the diagnosis and management of acute clinical deterioration in patients with late-stage Parkinson's disease. The authors outline common causes for such change and an approach to their workup and management. DISCUSSION: With an ageing population, we are seeing an increased prevalence of Parkinson's disease at all stages. Neurologists, geriatricians and GPs alike should therefore be familiar with the syndrome of late-stage Parkinson's disease and be equipped with treatment strategies to address acute non-motor and motor deteriorations.

A lack of association between increases in gastrointestinal, liver, and urologic cancers and cyanobacterial contamination of fresh water lakes in Manitoba.

Cyanobacteria or blue-green algae are becoming increasingly abundant in North American fresh water lakes. Toxins produced by cyanobacteria have been associated with gastrointestinal injury, liver failure, and nephrotoxicity. They have also been implicated in the pathogenesis of gastrointestinal and liver cancers. The purpose of the present study was to determine whether the incidence rates of gastrointestinal, liver, and urologic cancers are increasing in the province of Manitoba and, if so, whether these increases spatially and/or temporally correlate with areas where cyanobacterial contamination of fresh water lakes have been identified. Cancer incidence data were obtained from the Manitoba Cancer Registry. Cyanobacterial contamination data, as reflected by microcystin toxin concentrations, were available from the Manitoba Water Stewardship. ArcGIS mapping was employed to document spatial and temporal relationships between cancer incidence and cyanobacterial data. The results revealed that although the incidence rates for all three cancers have increased over the past 20-25 years, these increases were not disproportionally higher in zones with high microcystin toxin determinations. The results of this study argue against increased exposure to cyanotoxins as an explanation for the increase in gastrointestinal, liver and urologic cancers in Manitoba.

24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.

Levodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson's disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia. Clinical, demographic, dyskinesia rating scales were evaluated. Daytime dyskinesia was reduced in 75% (9/12) patients following treatment with 24-h therapy, including 7 who were compared with 16-h therapy and 2 that were transitioned from oral dopaminergic therapy to 24-h LCIG. Combining the data from all 12 subjects, troublesome dyskinesias were reduced during 24-h LCIG; UPDRS 4.1 (time spent with dyskinesias) mean change was -1.5 ± 0.75, p = 0.010 (Wilcoxon signed-rank test) and UPDRS 4.2 (functional impact of dyskinesias) mean change was -1.7 ± 0.90, p = 0.016, without changing their UPDRS part 3 "ON" scores (p = 0.138) or H&Y (p = 0.157). In 5 patients, improvement in dyskinesia occurred despite an overall increase in the total daily levodopa dose. None of the patients had worsening of dyskinesia after a median follow-up of 28 months. 24-h per day infusion of LCIG may be a useful strategy in the management of troublesome dyskinesias in PD patients with disabling dyskinesias resistant to attempts to optimise 16-hours per day therapy. We postulate that this may be due to a pharmacodynamic as opposed to pharmacokinetic mechanism.

Examining the impact of a province-wide physical education policy on secondary students' physical activity as a natural experiment.

BACKGROUND: The purpose of this paper is to examine the impact of a province-wide physical education (PE) policy on secondary school students' moderate to vigorous physical activity (MVPA). METHODS: Policy: In fall 2008, Manitoba expanded a policy requiring a PE credit for students in grades 11 and 12 for the first time in Canada. The PE curriculum requires grades 11 and 12 students to complete a minimum of 55 h (50% of course hours) of MVPA (e.g., ≥30 min/day of MVPA on ≥5 days a week) during a 5-month semester to achieve the course credit. STUDY DESIGNS: A natural experimental study was designed using two sub-studies: 1) quasi-experimental controlled pre-post analysis of self-reported MVPA data obtained from census data in intervention and comparison [Prince Edward Island (PEI)] provinces in 2008 (n = 33,619 in Manitoba and n = 2258 in PEI) and 2012 (n = 41,169 in Manitoba and n = 4942 in PEI); and, 2) annual objectively measured MVPA in cohorts of secondary students in intervention (n = 447) and comparison (Alberta; n = 224) provinces over 4 years (2008 to 2012). ANALYSIS: In Study 1, two logistic regressions were conducted to model the odds that students accumulated: i) ≥30 min/day of MVPA, and ii) met Canada's national recommendation of ≥60 min/day of MVPA, in Manitoba versus PEI after adjusting for grade, sex, and BMI. In Study 2, a mixed effects model was used to assess students' minutes of MVPA per day per semester in Manitoba and Alberta, adjusting for age, sex, BMI, school location and school SES. RESULTS: In Study 1, no significant differences were observed in students achieving ≥30 (OR:1.13, 95% CI:0.92, 1.39) or ≥60 min/day of MVPA (OR:0.92, 95% CI: 0.78, 1.07) from baseline to follow-up between Manitoba and PEI. In Study 2, no significant policy effect on students' MVPA trajectories from baseline to last follow-up were observed between Manitoba and Alberta overall (-1.52, 95% CI:-3.47, 0.42), or by covariates. CONCLUSIONS: The Manitoba policy mandating PE in grades 11 and 12 had no effect on student MVPA overall or by key student or school characteristics. However, the effect of the PE policy may be underestimated due to the use of a nonrandomized research design and lack of data assessing the extent of policy implementation across schools. Nevertheless, findings can provide evidence about policy features that may improve the PE policy in Manitoba and inform future PE policies in other jurisdictions.

Comparison of outcome of patients with CLL who are referred or nonreferred to a specialized CLL clinic: a Canadian population-based study.

Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) patients in Manitoba are either referred to the CLL Clinic at CancerCare Manitoba (CCMB) or are followed by other hematologists and general practitioners. However, it has been unclear whether referral to the CLL clinic influences patient outcome. Overall survival (OS) was assessed for all CLL/SLL patients diagnosed in Manitoba between 2007 and 2011. Of 555 patients, 281 (51%) were referred to the CLL clinic. Patients seen in this clinic had a twofold increased OS compared to patients who were managed by other hematologists and general practitioners (HR 2.375, P 0.0002) when adjusted for age, gender, presence of pre- or post-CLL cancer, treatment and urban/rural location. In the nonreferred population there was a striking correlation between advancing age and decreasing OS. However, this correlation was almost eliminated in the referred population who were more likely to receive chemotherapy. Patients referred and seen in the CLL clinic have an improved OS compared to nonreferred patients and this appears to be primarily related to improved OS in the elderly. Possible explanations for this finding are discussed.

Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease.

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from patients treated in a single Australian movement disorder centre. We conducted an open-label, 12 month prospective study of treatment with LCIG in patients with advanced Parkinson's disease in a single tertiary referral hospital unit specialising in movement disorders. Patients with levodopa-responsive, advanced Parkinson's disease with motor fluctuations despite optimal pharmacological treatment were enrolled and underwent a 16 hour daily infusion of LCIG for 12 months. Fifteen participants completed the trial. The mean (± standard deviation) improvement in Unified Parkinson's Disease Rating Scale part III was 37 ± 11%, mean daily "off" period reduced from 6.3 ± 2 to 1.9 ± 2 hours, total daily "on" time increased from 10.2 ± 3 to 13.7 ± 2 hours, "on" period without dyskinesia increased from 4.5 ± 3 to 7.5 ± 5 hours, and 39-item Parkinson's Disease Questionnaire Summary Index score improved by 32.5 ± 35%. The most common adverse event was reversible peripheral neuropathy secondary to vitamin B12 ± B6 deficiency (40%), local tube problems (40%), and impulse control disorder (ICD) (27%). No patient had stoma bleeding or peritonitis. All patients with ICD had a past psychiatric diagnosis of depression with or without anxiety and a higher daily levodopa intake at 6 and 12 months of LCIG infusion. Intraduodenal LCIG improves motor performance, quality of life and daily "on" period. Prior to and during duodenal LCIG infusion, clinicians should monitor for peripheral neuropathy and vitamin B12 and B6 deficiency, as supplementation can reverse peripheral neuropathy. This trial is registered at Clinicaltrials.gov as CT00335153.

The Geographic Distribution of Liver Cancer in Canada Does Not Associate with Cyanobacterial Toxin Exposure.

BACKGROUND: The incidence of liver cancer has been increasing in Canada over the past decade, as has cyanobacterial contamination of Canadian freshwater lakes and drinking water sources. Cyanotoxins released by cyanobacteria have been implicated in the pathogenesis of liver cancer. OBJECTIVE: To determine whether a geographic association exists between liver cancer and surrogate markers of cyanobacterial contamination of freshwater lakes in Canada. METHODS: A negative binomial regression model was employed based on previously identified risk factors for liver cancer. RESULTS: No association existed between the geographic distribution of liver cancer and surrogate markers of cyanobacterial contamination. As predicted, significant associations existed in areas with a high prevalence of hepatitis B virus infection, large immigrant populations and urban residences. DISCUSSION AND CONCLUSIONS: The results of this study suggest that cyanobacterial contamination of freshwater lakes does not play an important role in the increasing incidence of liver cancer in Canada.

Mammography rates for breast cancer screening: a comparison of First Nations women and all other women living in Manitoba, Canada, 1999-2008.

INTRODUCTION: First Nations (FN) women historically have low rates of preventive care, including breast cancer screening. We describe the frequency of breast cancer screening among FN women living in Manitoba and all other Manitoba (AOM) women after the introduction of a provincial, organized breast screening program and explore how age, area of residence, and time period influenced breast cancer screening participation. METHODS: The federal Indian Registry was linked to 2 population-based, provincial data sources. A negative binomial model was used to compare breast cancer screening for FN women with screening for AOM women. RESULTS: From 1999 through 2008, 37% of FN and 59% of AOM women had a mammogram in the previous 2 years. Regardless of area of residence, FN women were less likely to have had a mammogram than AOM women (relative rate [RR] = 0.69 in the north, RR = 0.55 in the rural south, and RR = 0.53 in urban areas). CONCLUSIONS: FN women living in Manitoba had lower mammography rates than AOM women. To ensure equity for all Manitoba women, strategies that encourage FN women to participate in breast cancer screening should be promoted.

24 h Levodopa-carbidopa intestinal gel may reduce falls and "unresponsive" freezing of gait in Parkinson's disease.

OBJECTIVE: We report a prospective, open label study of 24 h levodopa-carbidopa intestinal gel (LCIG) as treatment for levodopa "unresponsive" freezing of gait (FOG) associated with Parkinson's disease. METHOD: 5 patients with disabling FOG, documented as being levodopa "unresponsive", were commenced on continuous 24 h infusion LCIG therapy with the night-time rate at 50-80% of the daytime infusion rate. Patients underwent baseline, 3 and 6 month gait assessments, documentation of their falls frequency and completed FOG questionnaires. RESULT: Median 360° turn time improved by 54%, fall frequency score reduced from 3 to 0 at 6 months, FOG questionnaire score improved by 14% and Timed Up- and -Go 8 m walk was unchanged. CONCLUSION: 24 h LCIG therapy may reduce levodopa "unresponsive" FOG and associated falls. A larger prospective study is needed for confirmation.

Is the Provision of Physical Education to Senior-Years Students Associated With Greater Physical Activity Levels? Insight Into a Province-Wide Policy.

OBJECTIVES: The purpose of this study was to determine if participation in physical education (PE) was associated with increased moderate-to-vigorous physical activity (MVPA) levels in adolescents. METHODS: This was a cross sectional study comparing MVPA levels in senior-years students-grade 11 and 12-enrolled in high school PE during the semester data were collected compared with those not enrolled in PE in that same semester. The primary outcome measure was daily MVPA measured by accelerometry. The primary exposure was participation in PE. RESULTS: Among the 508 adolescents (16.9 ± 0.8 yrs, 49% female, n = 338 exposed to PE) studied, no differences in MVPA (47.0 ± 25.8 vs. 43.9 ± 25.0 mins/day, P = .25) or sedentary time (540.2 ± 94.7 vs. 550.2 ± 79.4 mins/day, P = .79) were noted between students enrolled in PE compared with students not enrolled in PE. Participation in PE was associated with a greater odds of achieving >60 minutes of MVPA daily (OR: 1.69; 95% CI: 1.04-2.75). This association was stronger among boys (OR: 2.4; 95% CI: 1.2-4.8) than girls (OR: 1.17; 95% CI: 0.5-2.7). CONCLUSION: Enrollment in PE in grade 11 or 12 is associated with modestly higher levels of MVPA and an increased likelihood of meeting PA guidelines among students in grades 11 and 12, particularly among boys.

Colorectal cancer screening in first nations people living in Manitoba.

BACKGROUND: Because the burden of colorectal cancer (CRC) seems to be increasing in First Nations, it is important to better understand CRC screening utilization. The objective of this study was to describe CRC screening among First Nations living in Manitoba. METHODS: The Federal Indian Register was linked to two provincial databases. A negative binomial model was used to compare the probability of First Nations having a fecal occult blood test (FOBT), colonoscopy, or flexible sigmoidoscopy (FS) with all other Manitobans. RESULTS: First Nations who lived in Winnipeg were significantly less likely to have had a FOBT in the previous 2 years than all other Manitobans who lived in Winnipeg [rate ratio (RR) = 0.40; 95% confidence intervals (CI), 0.37-0.44]. There was no difference in the likelihood of having a colonoscopy or FS for First Nations individuals who resided in northern Manitoba compared with all other Manitobans (RR, 1.04; 95% CI, 0.91-1.19). However, First Nations who lived in the rural south or urban areas were less likely than all other Manitobans to have had a colonoscopy or FS (RR, 0.81, 95% CI, 0.75-0.87, rural south; RR, 0.86, 95% CI, 0.81-0.92, urban). CONCLUSIONS: First Nations living in Winnipeg were significantly less likely to be screened for CRC using the FOBT. Colonoscopy and FS use depended on area of residence. IMPACT: First Nations experience barriers that impede the use of CRC screening. Further research is needed to understand these barriers to extend the benefit of CRC screening to this population. Cancer Epidemiol Biomarkers Prev; 24(1); 241-8. ©2014 AACR.

Pap test use and cervical cancer incidence in First Nations women living in Manitoba.

This study examined Papanicolaou (Pap) test utilization, Pap test results, and cervical cancer incidence among First Nations (FN) women living in Manitoba, Canada taking into account age group, time period, and area of residence. Six population-based data sources were linked at an individual level. Negative binomial regression was used to compare Pap test utilization and results between FN and all other Manitoba (AOM) women. Poisson regression was used to compare cervical cancer incidence. Among women younger than 25 years, FN were more likely than AOM women to have had a Pap test [rate ratio (RR) = 1.37, 95% confidence intervals (CI), 1.22-1.53, 18-19 year olds; RR = 1.17, 95% CI, 1.05-1.31, 20-24 year olds]. There was no difference in Pap test use for women 25 to 29 or 30 to 39 years. FN 40 years and older were less likely to have a Pap test than AOM women (RR = 0.84, 95% CI, 0.75-0.93, 40-49 years old; RR = 0.71, 95% CI, 0.63-0.79, 50-59 years old; RR = 0.59, 95% CI, 0.52-0.66, 60-69 years old). FN were more likely than AOM women to have a high (RR = 1.88, 95% CI, 1.65-2.13) or low-grade Pap test result (RR = 1.60, 95% CI, 1.48-1.73). The invasive cervical cancer incidence rate was double for FN women 25 to 39 years of age (21.9 per 100,000, FN; 10.2 per 100,000, AOM, P = 0.006) and 40 to 69 years of age (24.3 per 100,000, FN; 12.3 per 100,000, AOM, P = 0.007). In conclusion, cervical cancer screening among FN women over 40 years of age must be increased to address the higher cervical cancer incidence.

Geographical variation and factors associated with colorectal cancer mortality in a universal health care system.

OBJECTIVE: To investigate the geographical variation and small geographical area level factors associated with colorectal cancer (CRC) mortality. METHODS: Information regarding CRC mortality was obtained from the population-based Manitoba Cancer Registry, population counts were obtained from Manitoba's universal health care plan Registry and characteristics of the area of residence were obtained from the 2001 Canadian census. Bayesian spatial Poisson mixed models were used to evaluate the geographical variation of CRC mortality and Poisson regression models for determining associations with CRC mortality. Time trends of CRC mortality according to income group were plotted using joinpoint regression. RESULTS: The southeast (mortality rate ratio [MRR] 1.31 [95% CI 1.12 to 1.54) and southcentral (MRR 1.62 [95% CI 1.35 to 1.92]) regions of Manitoba had higher CRC mortality rates than suburban Winnipeg (Manitoba's capital city). Between 1985 and 1996, CRC mortality did not vary according to household income; however, between 1997 and 2009, individuals residing in the highest-income areas were less likely to die from CRC (MRR 0.77 [95% CI 0.65 to 0.89]). Divergence in CRC mortality among individuals residing in different income areas increased over time, with rising CRC mortality observed in the lowest income areas and declining CRC mortality observed in the higher income areas. CONCLUSIONS: Individuals residing in lower income neighbourhoods experienced rising CRC mortality despite residing in a jurisdiction with universal health care and should receive increased efforts to reduce CRC mortality. These findings should be of particular interest to the provincial CRC screening programs, which may be able to reduce the disparities in CRC mortality by reducing the disparities in CRC screening participation.

Enhancing capacity for risk factor surveillance at the regional/local level: a follow-up review of the findings of the Canadian Think Tank Forum after 4 years.

BACKGROUND: National health surveys are sometimes used to provide estimates on risk factors for policy and program development at the regional/local level. However, as regional/local needs may differ from national ones, an important question is how to also enhance capacity for risk factor surveillance regionally/locally. METHODS: A Think Tank Forum was convened in Canada to discuss the needs, characteristics, coordination, tools and next steps to build capacity for regional/local risk factor surveillance. A series of follow up activities to review the relevant issues pertaining to needs, characteristics and capacity of risk factor surveillance were conducted. RESULTS: Results confirmed the need for a regional/local risk factor surveillance system that is flexible, timely, of good quality, having a communication plan, and responsive to local needs. It is important to conduct an environmental scan and a gap analysis, to develop a common vision, to build central and local coordination and leadership, to build on existing tools and resources, and to use innovation. CONCLUSIONS: Findings of the Think Tank Forum are important for building surveillance capacity at the local/county level, both in Canada and globally. This paper provides a follow-up review of the findings based on progress over the last 4 years.