Ambikaipakan Senthilselvan

Clinical-pathological study of levodopa complications.

We sought to determine the continued benefit and the pattern of motor complications of long‐term levodopa treatment in Parkinsons disease. Patients were evaluated between 1968 and 1996. Only those who had an adequate levodopa trial and in whom autopsy revealed Lewy body Parkinsons disease were included. Total levodopa and mean daily dose were calculated in each case. Dyskinesia, wearing‐off and on‐off were collectively classified as motor adverse effects and reported as cumulative incidence. Forty‐two patients (male, 30; female, 12) with mean 15.9 years of illness and 9.1 years follow‐up received on average 500‐mg levodopa daily over 9.8 years. Seventeen of 21 patients assessed during the last 18 months of life reported some motor benefit. Adverse effects were seen in 71.4% of patients. The most common was dyskinesia, in 61.9%; wearing‐off in 35.7%; and on‐off in 16.7% of patients. The earliest adverse effect was dyskinesia and the last to emerge was on‐off. Isolated dyskinesia was seen in 35.7% and wearing‐off in 7.1% of patients; 15.5% of patients developed dyskinesia after 2.6 years and 31% after 6.4 years on levodopa. We concluded that levodopa benefit declined and adverse effects increased with time. Dyskinesia was the earliest and the most common isolated adverse effect.

How Well Are Hypertension, Hyperlipidemia, Diabetes, and Smoking Managed After a Stroke or Transient Ischemic Attack?

Background and Purpose— Stroke prevention clinics (SPCs) are not usually involved with the active management of hypertension, hyperlipidemia, diabetes, and smoking. The effect of consultations generated at SPCs on the adequacy of the management of these risk factors for stroke has not been well described, and few studies have long-term follow-up. Methods— We performed a prospective study of 119 consecutive patients referred to an SPC for secondary prevention. One year after their baseline visit, patients were re-evaluated for the adequacy of the management of the above risk factors, and the proportion of improvement was assessed. Results— One-hundred twelve patients returned for their 1-year follow-up visit. Sixty-six were male, and the average age was 65 years. Hypertension was present in 83 patients, hyperlipidemia in 92, diabetes in 26, and smoking in 38, and 80 had multiple risk factors. At baseline, 66% of patients with hypertension, 17% of patients with hyperlipidemia, and 23% of diabetics had adequate management of their respective risk factors. During 1 year of follow-up, hypertension management improved 20% (P <0.001) and lipid management improved 32% (P <0.001). There was no significant improvement in diabetes management or smoking cessation. Conclusions— Although our understanding of the benefit of addressing hypertension, hyperlipidemia, diabetes, and smoking for secondary prevention of stroke is evolving, we found marked room for improvement in the management of these four risk factors. SPCs may need to be more actively involved in the management of these modifiable risk factors, if we are to significantly impact the risk of recurrent stroke.

Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study.

OBJECTIVES The study objective was to evaluate the effects of sitagliptin in patients with type 2 diabetes (T2D) and heart failure (HF). BACKGROUND There is uncertainty in the literature about whether dipeptidyl peptidase (DPP)-4 inhibitors cause harm in patients with HF and T2D. METHODS We analyzed data from a national commercially insured U.S. claims database. Patients with incident HF were identified from individuals with T2D initially treated with metformin or sulfonylurea and followed over time. Subjects subsequently using sitagliptin were compared with those not using sitagliptin in the 90 days before our primary outcome of all-cause hospital admission or death using a nested case-control analysis after adjustment for demographics and clinical and laboratory data. HF-specific hospital admission or death also was assessed. RESULTS A total of 7,620 patients with diabetes and incident HF met our inclusion criteria. Mean (SD) age was 54 years (9), and 58% (3,180) were male. Overall, 887 patients (12%) were exposed to sitagliptin therapy (521 patient years of exposure) after incident HF. Our primary composite endpoint occurred in 4,137 patients (54%). After adjustment, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR]: 0.84, 95% confidence interval [CI]: 0.69 to 1.03) or each component (hospital admission 7.5% vs. 9.2%, aOR: 0.93, 95% CI: 0.76 to 1.14; death 6.9% vs. 9.3%, aOR: 1.16, 95% CI: 0.68 to 1.97). However, sitagliptin use was associated with an increased risk of HF hospitalizations (12.5% vs. 9.0%, aOR: 1.84, 95% CI: 1.16 to 2.92). CONCLUSIONS Sitagliptin use was not associated with an increased risk of all-cause hospitalizations or death, but was associated with an increased risk of HF-related hospitalizations among patients with T2D with pre-existing HF.

Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study

Objective To determine if the use of sitagliptin in newly treated patients with type 2 diabetes is associated with any changes in clinical outcomes. Design Retrospective population based cohort study. Setting Large national commercially insured US claims and integrated laboratory database. Participants Inception cohort of new users of oral antidiabetic drugs between 2004 and 2009 followed until death, termination of medical insurance, or December 31 2010. Main outcome measure Composite endpoint of all cause hospital admission and all cause mortality, assessed with time varying Cox proportional hazards regression after adjustment for demographics, clinical and laboratory data, pharmacy claims data, healthcare use, and time varying propensity scores. Results The cohort included 72 738 new users of oral antidiabetic drugs (8032 (11%) used sitagliptin; 7293 (91%) were taking it in combination with other agents) followed for a total of 182 409 patient years. The mean age was 52 (SD 9) years, 54% (39 573) were men, 11% (8111) had ischemic heart disease, and 9% (6378) had diabetes related complications at the time their first antidiabetic drug was prescribed. 14 215 (20%) patients met the combined endpoint. Sitagliptin users showed similar rates of all cause hospital admission or mortality to patients not using sitagliptin (adjusted hazard ratio 0.98, 95% confidence interval 0.91 to 1.06), including patients with a history of ischemic heart disease (adjusted hazard ratio 1.10, 0.94 to 1.28) and those with estimated glomerular filtration rate below 60 mL/min (1.11, 0.88 to 1.41). Conclusions Sitagliptin use was not associated with an excess risk of all cause hospital admission or death compared with other glucose lowering agents among newly treated patients with type 2 diabetes. Most patients prescribed sitagliptin in this cohort were concordant with clinical practice guidelines, in that it was used as add-on treatment.

Social, Demographic, and Health Outcomes in the 10 Years Following Adolescent Depression

PURPOSE Little attention has been paid to the sociodemographic profiles of depressed youth during the vulnerable transition from adolescence to early adulthood. This study aimed to determine and describe the social, demographic, and health outcomes of adolescent depression during a 10-year period of transition into early adulthood, using a population-based cohort of Canadian teenagers. METHODS Depression status on 1,027 adolescents aged 16-17 years was ascertained from the National Population Health Survey. Social and health outcomes (i.e., employment status, marital status, personal income, education, social support, self-perceived stress, heavy drinking, smoking, migraine headaches, adult depression, antidepressant use, self-rated health, and physical activity) were measured every 2 years until the ages of 26-27 years. Logistic regression was combined with a generalized linear mixed-model approach to determine the odds of health and social outcomes in depressed versus nondepressed adolescents. RESULTS Proximal effects of adolescent depression were observed (at ages 18-19) on all outcomes with the exception of physical activity. Significant effects that persisted after 10 years included depression recurrence, higher severity of symptoms, migraine headaches, poor self-rated health, and low levels of social support. Adolescent depression did not appear to significantly affect employment status, personal income, marital status, or educational attainment. CONCLUSIONS The transition from adolescence to adulthood is a particularly vulnerable period due to educational, employment, and social changes that may be occurring. The results of this study indicate that the onset of depression during adolescence may be indicative of problems of adaptation that persist at least a decade into early adulthood.

Total dust and endotoxin in poultry operations: comparison between cage and floor housing and respiratory effects in workers.

Objective: The objective of this study was to assess respiratory outcomes and environmental exposure levels of workers in cage-housed and floor-housed poultry operations. Methods: Poultry operations were evaluated for total dust, endotoxin, and ammonia, and respiratory symptoms and lung function tests of workers were conducted. Results: Workers in floor-housed poultry operations had significantly greater exposures to total dust and ammonia, whereas workers from cage-housed poultry operations reported greater frequency of current and chronic symptoms overall and significantly greater current and chronic phlegm (39% vs 18% and 40% vs 11%, respectively). Endotoxin concentration (EU/mg) was a significant predictor (P = 0.05) of chronic phlegm for all poultry workers. Conclusions: Greater endotoxin concentration in the presence of significantly lower total dust, in conjunction with greater respiratory symptoms in workers from cage-housed poultry operations, as compared with workers from floor-housed poultry operations, appears to indicate that differences in environmental exposures may impact respiratory outcomes of workers.

Predictors of long-term prognosis of depression

Background: Many people with depression experience repeated episodes. Previous research into the predictors of chronic depression has focused primarily on the clinical features of the disease; however, little is known about the broader spectrum of sociodemographic and health factors inherent in its development. Our aim was to identify factors associated with a long-term negative prognosis of depression. Methods: We included 585 people aged 16 years and older who participated in the 2000/01 cycle of the National Population Health Survey and who reported experiencing a major depressive episode in 2000/01. The primary outcome was the course of depression until 2006/07. We grouped individuals into trajectories of depression using growth trajectory models. We included demographic, mental and physical health factors as predictors in the multivariable regression model to compare people with different trajectories. Results: Participants fell into two main depression trajectories: those whose depression resolved and did not recur (44.7%) and those who experienced repeated episodes (55.3%). In the multivariable model, daily smoking (OR 2.68, 95% CI 1.54–4.67), low mastery (i.e., feeling that life circumstances are beyond one’s control) (OR 1.10, 95% CI 1.03–1.18) and history of depression (OR 3.5, 95% CI 1.95–6.27) were significant predictors (p < 0.05) of repeated episodes of depression. Interpretation: People with major depression who were current smokers or had low levels of mastery were at an increased risk of repeated episodes of depression. Future studies are needed to confirm the predictive value of these variables and to evaluate their accuracy for diagnosis and as a guide to treatment.

Asthma presentations by adults to emergency departments in Alberta, Canada: a large population-based study

BACKGROUND Asthma is a widespread disease with a prevalence of approximately 7 to 10% in adults. Exacerbations are common in the emergency department (ED) setting. The objective of this study was to describe the epidemiology of asthma presentations to EDs made by adults in the province of Alberta, Canada. METHODS The Ambulatory Care Classification System of Alberta and provincial administrative databases were used to obtain all ED encounters for asthma during 6 fiscal years (April 1999 to March 2005). Information extracted included demographics, ED visit timing, and subsequent visits to non-ED settings. Data analysis included descriptive summaries and directly standardized visit rates. RESULTS There were 105,813 ED visits for asthma made by 48,942 distinct adults, with an average of 2.2 visits per individual. Most patients (66%) had only one asthma-related ED visit. Female patients (61.2%) presented more commonly than male patients. The gender- and age-standardized visit rates declined from 9.7/1,000 in 1999/2000 to 6.8/1,000 in 2004/2005. The welfare and Aboriginal subsidy groups had larger age-specific ED visits rates than other populations. Important daily, weekly, and monthly trends were observed. Hospital admission occurred in 9.8% of the cases; 6.4% had a repeat ED visit within 7 days. Overall, 67.4% of individuals had yet to have a non-ED follow-up visit by 1 week. The estimated median time to the first follow-up visit was 19 days (95% confidence interval, 18 to 21). CONCLUSIONS Asthma is a common presenting problem in Alberta EDs, and further study of these trends is required to understand the factors associated with the variation in presentations. The important findings include an overall decrease in the rates of presentation over the study period, disparities based on age, gender, and socioeconomic/cultural status, and the low rate of early follow-up. Targeted interventions could be implemented to address specific groups and reduce asthma-related visits to Alberta EDs.

Occupational Pesticide Exposures and Respiratory Health

Pesticides have been widely used to control pest and pest-related diseases in agriculture, fishery, forestry and the food industry. In this review, we identify a number of respiratory symptoms and diseases that have been associated with occupational pesticide exposures. Impaired lung function has also been observed among people occupationally exposed to pesticides. There was strong evidence for an association between occupational pesticide exposure and asthma, especially in agricultural occupations. In addition, we found suggestive evidence for a link between occupational pesticide exposure and chronic bronchitis or COPD. There was inconclusive evidence for the association between occupational pesticide exposure and lung cancer. Better control of pesticide uses and enforcement of safety behaviors, such as using personal protection equipment (PPE) in the workplace, are critical for reducing the risk of developing pesticide-related symptoms and diseases. Educational training programs focusing on basic safety precautions and proper uses of personal protection equipment (PPE) are possible interventions that could be used to control the respiratory diseases associated with pesticide exposure in occupational setting.

Assessment of endotoxin levels in the home and current asthma and wheeze in school-age children

UNLABELLED The relationship between household endotoxin and asthma in children is not clear. To further investigate the relationship between sources of endotoxin and childhood asthma, we conducted a case-control study of children with and without asthma and examined their more frequent household exposures in the home. Children ages 6-13 years with current asthma (n = 70) or wheeze only (n = 19) were sex and age matched (+/-1 year) to 107 controls. Play area and mattress dust were collected for endotoxin analysis. Atopic status was determined by skin prick testing for allergies. A family size of >4 per household was associated with higher endotoxin levels (EU/mg) in the bed dust (P < 0.05). Passive smoking (P < 0.05) and the presence of a cat were associated with higher levels of endotoxin in mattress dust. Endotoxin levels in either the play dust or the bed dust did not differ between cases and controls. Within atopic cases, those with higher endotoxin loads (EU/m2) in bed or play areas were more likely to miss school for chest illness (P < 0.05). In this study, household endotoxin is not a risk factor for current asthma overall but may be associated with increased severity in children with atopic asthma. PRACTICAL IMPLICATIONS This study did not find that household sources of endotoxin were associated with asthma. However, within atopic asthmatics, asthma severity (as measured by a history of being kept home from school because of a chest illness in the past year) was associated with higher levels of endotoxin in dust from the childs bed. There is a need to further investigate the nature of the relationship between household endotoxin and asthma severity in children which could lead to better management of childhood asthma.