Increased Vascular Pathology in Older Veterans With a Purple Heart Commendation or Chronic Post-Traumatic Stress Disorder.

The goal of this retrospective cohort study was to determine whether stressors related to military service, determined by a diagnosis of chronic post-traumatic stress disorder (cPTSD) or receiving a Purple Heart (PH), are associated with an increased risk of vascular risk factors and disease, which are of great concern for veterans, who constitute a significant portion of the aging US population. The Veterans Integrated Service Network (VISN) 16 administrative database was searched for individuals 65 years or older between October 1, 1997 to September 30, 1999 who either received a PH but did not have cPTSD (PH+/cPTSD-; n = 1499), had cPTSD without a PH (PH-/cPTSD+; n = 3593), had neither (PH-/cPTSD-; n = 5010), or had both (PH+/cPTSD+; n = 153). In comparison to the control group (PH-/cPTSD-), the PH+/cPTSD- group had increased odds ratios for incidence and prevalence of diabetes mellitus, hypertension, and hyperlipidemia. The PH-/cPTSD+ group had increased odds ratios for prevalence of diabetes mellitus and for the incidence and prevalence of hyperlipidemia. The PH-/cPTSD+ and PH+/cPTSD- groups were associated with ischemic heart disease and cerebrovascular disease, but not independently of the other risk factors. The PH+/cPTSD+ group was associated only with an increase in the incidence and prevalence of hyperlipidemia, though this group's much smaller sample size may limit the reliability of this finding. We conclude that certain physical and psychological stressors related to military service are associated with a greater incidence of several vascular risk factors in veterans aged 65 years or older, which in turn are associated with greater rates of ischemic heart disease and cerebrovascular disease.

High Prevalence of Stroke in Rural Gadchiroli, India: A Community-Based Study.

BACKGROUND: In the near future, a majority of strokes are projected to occur in developing countries. However, population-level information on the prevalence of stroke from rural areas of developing countries, including India, is rare. We estimated the prevalence of stroke in a rural area of one of the most underdeveloped districts of India. METHODS: Trained surveyors conducted a house-to-house survey using a validated screening questionnaire in a well-defined population of 45,053 living in 39 villages in a demographic surveillance site in Gadchiroli district. A trained physician and a neurologist evaluated screen-positive patients and diagnosed stroke using the World Health Organization's criteria. RESULTS: In the screened population, 175 patients had stroke. The mean age of patients with stroke was 60.9 ± 14.7 years and 32.5% were women. The crude prevalence rate of stroke was 388.43 (95% CI 335.04-450.33) and the age-standardized prevalence rate of stroke was 535.58 (95% CI 492.41-583.01) per 100,000 population. The crude prevalence rate of stroke was significantly higher among men than among women (520 vs. 255/100,000 population, p < 0.05). CONCLUSION: In this prevalence study, conducted after a gap of 20 years in rural India, the prevalence of stroke was high and was more than twice the prevalence reported from the previous study. The prevalence was double among men compared to women. Stroke is emerging as a public health priority in rural India.

Stroke Is the Leading Cause of Death in Rural Gadchiroli, India: A Prospective Community-Based Study.

BACKGROUND AND PURPOSE: Stroke is an important cause of death and disability worldwide. However, information on stroke deaths in rural India is scarce. To measure the mortality burden of stroke, we conducted a community-based study in a rural area of Gadchiroli, one of the most backward districts of India. METHODS: We prospectively collected information on all deaths from April 2011 to March 2013 and assigned causes of death using a well-validated verbal autopsy tool in a rural population of 94 154 individuals residing in 86 villages. Two trained physicians independently assigned the cause of death, and the disagreements were resolved by a third physician. RESULTS: Of 1599 deaths during the study period, 229 (14.3%) deaths were caused by stroke. Stroke was the most frequent cause of death. For those who died because of stroke, the mean age was 67.47±11.8 years and 48.47% were women. Crude stroke mortality rate was 121.6 (95% confidence interval, 106.4-138.4), and age-standardized stroke mortality rate was 191.9 (95% confidence interval, 165.8-221.1) per 100,000 population. Of total stroke deaths, 87.3% stroke deaths occurred at home and 46.3% occurred within the first month from the onset of symptoms. CONCLUSIONS: Stroke is the leading cause of death and accounted for 1 in 7 deaths in this rural community in Gadchiroli. There was high early mortality, and the mortality rate because of stroke was higher than that reported from previous studies from India. Stroke is emerging as a public health priority in rural India.

Surveillance of stroke: a South-East Asia Region (SEAR) perspective.

Surveillance of stroke is critical to track its burden and assess progress in prevention and treatment. We reviewed the literature to evaluate stroke surveillance efforts in the South-East Asia Region (SEAR) countries, identify progress and assess gaps. Epidemiological data on all the major parameters such as the incidence, prevalence and mortality of stroke were available for India and Thailand but for none of the other SEAR countries. Most of the epidemiological data came from investigator-initiated studies. National stroke surveillance was present only in India in the form of a National Stroke Registry Programme and Thailand has a national database that was used to obtain epidemiological data for stroke. Research on novel methods for stroke registration, such as using information technology, was absent. This review identified serious gaps in the monitoring and surveillance of stroke in SEAR countries. Systematic efforts are needed to fill those gaps.

The burden, risk factors and unique etiologies of stroke in South-East Asia Region (SEAR).

The World Health Organization (WHO) South East Asia Region (SEAR) comprises 11 countries, which are one of the most culturally, topographically, and socially diverse areas worldwide, undergoing an epidemiological transition towards non-communicable diseases, including stroke and other cardiovascular diseases (CVDs). This region accounts for over 40% of the global stroke mortality. Few well-designed population-based epidemiological studies on stroke are available from SEAR countries, with considerable variations among them. Ischemic stroke, a common stroke subtype, has higher frequencies of intracerebral hemorrhage in many countries. Along with an aging population, the increased prevalence of risk factors such as hypertension, diabetes mellitus, tobacco and alcohol consumption, lack of physical activity, high ambient pollution, heat, and humidity contribute to the high burden of stroke in this region. SEAR's many unique and uncommon stroke etiologies include cerebral venous thrombosis, tuberculosis, dengue, scrub typhus, falciparum malaria, snake bite, scorpion sting, etc. Current data on stroke burden and risk factors is lacking, compelling an urgent need for high-quality hospital-level and population-level data in all SEAR countries. Strategies towards a consolidated approach for implementing improved stroke prevention measures, stroke surveillance, and established stroke systems of care are the path to bridging the gaps in stroke care.

Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities.

The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.

Medical and environmental risk factors associated with frontotemporal dementia: a case-control study in a veteran population.

BACKGROUND: Compared with other major dementias, very little is known about the medical and environmental risk factors associated with frontotemporal dementia (FTD). In this study, we evaluated medical and environmental disorders associated with FTD in a veteran population. METHODS: The medical records of 845 consecutive veterans who were evaluated for cognitive and/or behavioral complaints at a cognitive disorders clinic in an academic medical center between March 1, 2003, and June 30, 2008, were reviewed and 554 patients received a diagnosis of dementia. Medical disorders and environmental risk factors in 63 patients with behavioral variant of FTD were compared with 491 patients with non-FTD dementias. RESULTS: The prevalence of traumatic brain injury (TBI) was significantly greater in patients with FTD versus those with non-FTD dementias (12.7% vs 3.5%; P < .05). The FTD group also had a lower prevalence of heart disease (19.0% vs 36.7%; P < .05) and cerebrovascular diseases (12.7% vs 26.1%; P < .05), although the prevalence of vascular risk factors was comparable between FTD and non-FTD dementia groups: hypertension (65.1% vs 68.2%), diabetes (31.7% vs 26.9%), hyperlipidemia (42.9% vs 48.9%), and tobacco use (7.9% vs 8.8%; P > .05 for all). In multivariate analysis, the risk for FTD was increased in patients with TBI (OR, 4.4; 95% CI, 1.6-11.8). The risk for FTD was marginally decreased in patients with heart disease (OR, 0.4; 95% CI, 0.3-0.96). CONCLUSIONS: In a clinical sample of veterans, risk of FTD was increased in patients with TBI and marginally decreased in patients with heart disease. Prospective studies are needed to confirm these associations temporally and to identify their underlying mechanisms.

Clinical patterns and their prevalence among adult population with back pain: A community-based cross-sectional study in rural Gadchiroli, India.

BACKGROUND: Evaluating clinical patterns and their prevalence of back pain, a common problem in rural areas, can help develop treatment strategies to address this leading cause of disability. METHODS: We conducted a population-based study in rural Gadchiroli, India. In this, two-phase study, trained surveyors conducted a door to door survey (Phase 1) to identify individuals with pain in the back and extremities in two villages randomly selected using pre-defined criteria. Those with pain were evaluated by a team of spine surgeons and rheumatologists to diagnose clinical conditions among these patients (Phase 2). RESULTS: Of the 2535 eligible adults, 2259 (89%) were screened, 1247 (55%) reported pain in back and limb and were referred to the specialist clinic. Out of the 906 (73%) participants who attended the clinics, 783 (89%) had back/neck pain. The point prevalence of back/neck pain among adults was 49% (95% confidence interval (CI) = 49%-51%), non-specific low back pain 45% (95% CI = 43.4%-47.5%); non-specific neck pain 21% (95% CI = 18.9-22.4), radiculopathy 12 (95% CI = 10.4-13.1), myelopathy 0.4 (95% CI = 0.1-0.7) and other serious spinal disorders 0.2 (95% CI 0.048-0.45). The prevalence of non-specific back/neck pain and radiculopathy was higher among females. CONCLUSIONS: Non-specific back and neck pain are the commonest diagnoses among those with pain in the back and extremities, followed by radiculopathy. Serious disorders are rare. Given the high prevalence of non-specific back and neck pain, community health workers and physicians working in rural areas need to be trained systematically to manage these conditions.

A matching algorithm to address imbalances in study populations: application to the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator acute stroke trial.

BACKGROUND AND PURPOSE: Outcome from stroke is highly dependent on baseline conditions. Patients with stroke have a wide range of severities, ages, and etiologies and it has proven difficult to achieve randomization of key variables in clinical trials. We present a new post hoc approach to achieve balance among selected variables. To illustrate the approach, we rebalanced the National Institute of Neurological Diseases and Stroke Recombinant Tissue Plasminogen Activator trial, in which the contribution of baseline imbalances continues to be debated. METHODS: We selected baseline stroke severity (National Institutes of Health Stroke Scale), age, and glucose as matching criteria. The closest matched placebo and treated subjects were identified based on nearness to each other in 3-dimensional Euclidean space. Matching was performed within the quintiles of National Institutes of Health Stroke Scale that have been previously used to assess balance. Subjects who could not be matched were eliminated. Outcomes were assessed using the original specified National Institute of Neurological Diseases and Stroke trial measures. RESULTS: We successfully matched the 2 arms resulting in nearly identical baseline characteristics and distribution among quintiles. Despite fewer subjects after outlier elimination, the primary outcome measures remained significantly improved. After rebalancing, the magnitude of benefit was reduced by 13% to 23%. Benefit was apparent mostly in the large vessel occlusion subtype. CONCLUSION: This study demonstrated the feasibility of rebalancing individual subjects within a randomized trial. After rebalancing and outlier elimination, recombinant tissue plasminogen activator continued to demonstrate improved outcome. That the apparent treatment effect was reduced suggests that imbalances contributed to the magnitude of the original National Institute of Neurological Diseases and Stroke outcomes. This method could in theory be applied to any data set to find matched subjects for outcome or other analyses.

Differences between clinical subspecialties in the outpatient evaluation and treatment of dementia in an academic medical center.

BACKGROUND: Professional organizations have recommended guidelines for the optimal investigation and management of dementia. It is unknown whether physicians from different subspecialties investigate and treat dementia in the same manner or according to these guidelines. METHODS: We screened 1,401 charts of patients who were seen in neurology, mental health, geropsychiatry and geriatrics clinics. The charts of 410 patients who were diagnosed with dementia were reviewed in detail to determine how they were evaluated and managed. RESULTS: Overall, 40% of patients received a complete laboratory workup to rule out comorbidities, 70% of patients received neuroimaging with either computerized tomography or magnetic resonance imaging of the brain, 63% had a depression screen and 38% of patients underwent neuropsychological testing. However, the frequency with which they were obtained differed significantly across clinics (p < 0.05). The frequency with which acetylcholinesterase inhibitors (CHEIs) were used did not differ significantly (p = 0.07) for patients with Alzheimer's disease (AD), but differed significantly (p < 0.05) for dementia categories where CHEIs are thought to be useful (AD, vascular dementia and dementia with Lewy bodies). CONCLUSIONS: There were significant differences between subspecialties in the evaluation and treatment of dementia. It will be important to investigate whether these differences alter patient outcomes.

Non-communicable diseases are the leading cause of mortality in rural Birbhum, West Bengal, India: a sex-stratified analysis of verbal autopsies from a prospective cohort, 2012-2017.

OBJECTIVES: There is a dearth of data on causes of death in rural India, which impedes identification of public health priorities to guide health interventions. This study aims to offer insights from verbal autopsies, to understand the pattern and distribution of causes of death in a rural area of Birbhum District, West Bengal, India. DESIGN: Causes of death data were retrieved from a prospective vital event surveillance system. SETTING: The Birbhum Population Project, a Health and Demographic Surveillance System, West Bengal, India. PARTICIPANTS: Between January 2012 and December 2017, all deaths were recorded. MAIN OUTCOME MEASURES: Trained Surveyors tracked all deaths prospectively and used a previously validated verbal autopsy (VA) tool to record causes of death. Experienced physicians reviewed completed VA forms, and assigned cause of death using the 10th version of International Classification of Diseases. In addition to cause-specific mortality fraction, cause-specific crude death rate (CDR) among males and females were estimated. RESULTS: A total of 2320 deaths (1348 males and 972 females) were recorded. An estimated CDR was 708/100 000. Over half of all deaths (1176 deaths, 50.7%) were attributed to non-communicable diseases (NCDs), with nearly 30% of all deaths attributed to circulatory system disorders; whereas 24.2% and 3.9% deaths were due to cerebrovascular diseases and ischaemic heart disease, respectively. Equal percent (13%) of males died from external causes and from infectious and parasitic diseases, and 11% died from respiratory system-related diseases. Among females, 12% died from infectious and parasitic diseases. Among children aged 0-4 years, 50% of all male deaths and 45% of all female deaths were attributed to conditions in the perinatal period. CONCLUSIONS: NCDs are the leading cause of death among adults in a select population of rural Birbhum, India. Health programmes for rural India should prioritise plans to mitigate deaths due to NCDs.

Ethnic disparities in the treatment of dementia in veterans.

OBJECTIVES: To test for ethnic disparities in the evaluation and treatment of dementia. METHODS: We reviewed 1,401 charts of patients from 4 veteran clinics that routinely evaluate dementia patients. A total of 410 patients met criteria for dementia or mild cognitive impairment (MCI) and their charts were reviewed in detail. RESULTS: Regarding their evaluation, laboratory and imaging testing did not differ between ethnic groups (p > 0.05). Depression screening was more common in African-American (AA) patients (p = 0.03). Significantly more Caucasian patients underwent neuropsychologic testing (p = 0.001). Regarding management, in a multivariate analysis, AA patients with Alzheimer's disease (AD) (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.5) or 'all dementia types' (OR 0.6, 0.3-0.9) were significantly less likely to receive acetylcholinesterase inhibitors (CHEIs). Other independent predictors of CHEI use were age >or=71 years (OR 5.2, 2.8-9.6), a diagnosis of AD (OR 3.1, 1.6-6.3) or MCI (OR 0.3, 0.1-0.7), and if their evaluation included imaging (head CT or MRI; OR 1.9, 1.05-3.3). CONCLUSIONS: AA patients underwent comparable evaluations for dementia and the percentage of CHEI-responsive diagnoses rendered was similar across ethnic groups. However, dementia management differed significantly: AAs were prescribed CHEIs at considerably reduced rates. The reasons for this great disparity warrant further investigation because it may produce significantly greater cognitive impairment and hence suffering amongst AA patients.

Divergent trends in ischaemic heart disease and stroke mortality in India from 2000 to 2015: a nationally representative mortality study.

INTRODUCTION: India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. METHODS: We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. FINDINGS: Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30-69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000-15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India's population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. INTERPRETATION: The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. FUNDING: Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities.

Chemokines in the MPTP model of Parkinson's disease: absence of CCL2 and its receptor CCR2 does not protect against striatal neurodegeneration.

Recent studies have invoked inflammation as a major contributor to the pathogenesis of Parkinson's disease (PD). We determined the role of members of the chemokine system, key inflammatory mediators, in PD pathogenesis. In the MPTP model of murine PD, several chemokines, including CC chemokine ligand 2 (CCL2, Monocyte Chemoattractant Protein-1) and CCL3 (Macrophage Inflammatory Protein-1alpha), were upregulated in the striatum and the ventral midbrain. Astrocytes were the predominant source of CCL2 and CCL3 in the striatum and the substantia nigra, and dopaminergic neurons in the substantia nigra constitutively expressed these two chemokines. MPTP treatment resulted in decreased CCL2 expression and increased CCL3 expression in the surviving dopaminergic neurons. Because we found that CCL2 induced production of TNF-alpha in microglial cells, a cytokine known to play a detrimental role in PD, we anticipated that deletion of the genes encoding CCL2 and CCR2, its major receptor, would confer a protective phenotype. However, MPTP-induced striatal dopamine depletion was comparable in double knockout and wild-type mice. Our results demonstrate that chemokines such as CCL2 are induced following MPTP treatment, but that at least within the context of this PD model, the absence of CCL2 and CCR2 does not protect against striatal dopamine loss.

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification.

BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that--assuming each molecular biomarker to be a diagnostic test--enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i) subjects having cancer with those without; ii) subjects with two different cancers; iii) subjects with two different types of one cancer; and iv) subjects with same cancer resulting in differential time to metastasis. RESULTS: Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

Healthcare seeking behavior for back and joint pain in rural gadchiroli, India: a population-based cross-sectional study.

BACKGROUND: Musculoskeletal back and joint pain is common in rural agrarian communities in India. OBJECTIVES: To understand the healthcare seeking behavior for back and joint pain among adults in rural Gadchiroli, India. MATERIALS AND METHODS: A cross-sectional survey of 315 randomly selected respondents from 84 villages between 30 and 60 years of age was conducted by community health workers (CHWs) between October 2010 and January 2011. RESULTS: Among 280 respondents on whom good quality data were available, 215 (76.8%) respondents had back and/or joint pain in 6 months preceding the survey. A majority of the respondents with pain had sought care (170; 79.1%), mainly from private practitioners (116; 68.2%). Severe pain and inability to work were the reasons to seek care. Complete pain relief was considered the major indicator of an effective treatment. Injectable medications (127; 59.1%) and intravenous fluids (92; 42.8%) were considered highly effective; while about 50% were unaware of the role of physiotherapy and surgery for this problem. When asked about the preferred provider who should provide village level treatment of this problem, more than half (135; 62.8%) of the respondents chose a trained village health worker. CONCLUSIONS: A majority of the individuals with back and/or joint pain in rural Gadchiroli seek care, mainly from private practitioners. However, for the village-level treatment of this problem, respondents preferred a trained village level worker. High expectation of complete pain relief, preference for injectable medications, and low awareness about nonpharmacological modalities will be the major challenges while providing community level care for this problem.

A case of severe chronic progressive axonal polyradiculoneuropathy temporally associated with anti-CV2/CRMP5 antibodies.

OBJECTIVES: The involvement of the peripheral nervous system by anti-CV2/CRMP5 paraneoplastic antibodies is typically encountered as a mixed sensorimotor polyneuropathy. We report a fatal case of severe chronic progressive axonal polyradiculoneuropathy in association with this antibody. METHODS: Review of the patient's chart, nerve conduction/electromyographic studies, and nerve biopsy. RESULTS: A 51-year-old man presented with a progressive quadriparesis over a 4-month period. Extensive evaluation for potential etiologies was significant only for positive anti-CV2/CRMP5 antibodies without detection of an underlying neoplasm. Despite multiple immunomodulatory therapies, the patient progressed and demonstrated electrodiagnostic evidence for a chronic axonal polyradiculoneuropathy with ongoing denervation. The patient eventually died of respiratory failure. CONCLUSIONS: This case adds to the clinical spectrum of the peripheral nervous system involvement in patients with paraneoplastic anti-CV2/CRMP5 antibodies.