Aproximações entre as antropologias de Cecil Helman e Clifford Geertz / Aproximaciones entre las antropologías de Cecil Helman y Clifford Geertz / Approaches between the anthropologies of Cecil Helman and Clifford Geertz

This article aims to promote conceptual exploration in the literature of Medical Anthropology or Health and Interpretative Anthropology, approaching the perspectives of Clifford JamesGeertz and Cecil Helman. The segmented three-axis approach reflects some perspectives on thekey concepts of culture and ethnography. It was also evident from the impasses generated by theacademic effort of the medical system when studying other care systems, a clear tendency to resortto generalizations, stratigraphic conception and consensus gentium, typical of colonialist ethnography, addressing the ethical commitment and self-reflexivity of the researcher as solution. It endswith an approximation between Cecil Helman's theories on causes of illness and Clifford Geertz'sknowledge and interpretation of the senses, values, behaviors and local knowledge. Therefore, webelieve that the article complements the debates in the area of ethnography, meanings of illness and health, standardized in the Anthropology of Health-disease. (AU)

Este artículo tiene como objetivo promover la exploración conceptual en la literatura deAntropología Médica o Antropología de la Salud e Interpretativa, reuniendo las perspectivas deClifford James Geertz y Cecil Helman. El enfoque segmentado de tres ejes refleja algunas tivas sobre los conceptos clave de cultura y etnografía. También fue evidente por los impases generados por el esfuerzo académico del sistema médico al estudiar otros sistemas de atención, una claratendencia a recurrir a generalizaciones, concepción estratigráfica y consensus gentium, típico de laetnografía colonialista, abordando el compromiso ético y la autorreflexividad de investigador comosoluciones. Termina con una aproximación entre las teorías de Cecil Helman sobre las causas de laenfermedad y el conocimiento e interpretación de Clifford Geertz de los sentidos, valores, comportamientos y conocimiento local. Por lo tanto, creemos que el artículo complementa los debates en el área de etnografía, sentidos de la enfermedad y salud, estandarizados en la Antropología de la Salud-enfermedad. (AU)

Este artigo tem como objetivo promover exploração conceitual na literatura de Antropologia Médica ou da Saúde e Antropologia Interpretativa, aproximando as perspectivas de CliffordJames Geertz e Cecil Helman. A abordagem segmentada em três eixos reflete algumas perspectivassobre os conceitos-chave cultura e etnografia. Evidenciou-se ainda a partir dos impasses geradospelo esforço acadêmico do sistema médico ao estudar outros sistemas de cuidado, clara tendência arecorrer a generalizações, concepção estratigráfica e consensus gentium, típicos da etnografia colonialista, abordando-se o compromisso ético e a autorreflexividade do pesquisador como soluções.Encerra-se com uma aproximação entre as teorias sobre causas do adoecimento de Cecil Helman eo conhecimento e interpretação dos sentidos, valores, condutas e saber local de Clifford Geertz. Diante disso, acreditamos que o artigo complementa os debates na área da etnografia, sentidos do adoecimento e saúde, estandardizados na Antropologia da Saúde-doença. (AU)

Home parenteral nutrition and employment in patients with intestinal failure: Factors associated with return to employment.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is provided to patients with intestinal failure (IF). HPN can however affect the patients' quality of life and ability to remain in employment. The aim of this study was to determine the effect of HPN on employment and factors associated with the likelihood of maintaining or returning to employment while on HPN. METHODS: Patients with chronic IF were identified from a prospectively maintained IF Unit database. A structured questionnaire was designed to probe employment both before and after starting HPN, intention to work and social welfare status (benefits & pensions). RESULTS: A total of 196 (62.8% females, median age 53 years) patients participated in the study of which 184 (94%) patients were in full or part time employment before their illness. At the time of starting HPN, 102 (52%) patients had the desire to return to work with 19 (18%) and 48 (47%) patients returning to full time or part time employment respectively. Multivariate analysis demonstrated that the frequency of the HPN infusion per week (p = 0.045) and intention to work after starting HPN (p = 0.001) were significantly associated with returning to work. CONCLUSIONS: Patients on HPN can have their employment status affected. The number of days per week on HPN and the desire of the patient to return to employment are significantly associated with employment.

Completeness in clerking: The surgical admissions proforma.

BACKGROUND: The accessibility of surgical patient data is a key safety concern, and relies on efficient clerking and handovers. This project assessed whether the introduction of a surgical clerking proforma improved the recording of patient information in the surgical admissions unit (SAU) at Northwick Park Hospital. MATERIALS AND METHODS: Existing patient notes were assessed on content and ease of access, using two independent surveys conducted over a 5-day period. The first survey audited patient notes before (n = 28) and after (n = 23) the introduction of the proforma. It assessed whether key patient details were documented, in line with the 17 criteria set out in the Guidelines for Clinicians on Medical Records and Notes by The Royal College of Surgeons in England. The second survey questioned healthcare professionals before (n = 25) and after (n = 17) proforma implementation on the accessibility of patient data and coherency of patient notes. RESULTS: 5 of the 17 criteria showed significant differences post proforma implementation. Of these differences, the recording of height and occupation was most notable (p < 0.01). Medication history, weight and investigations also showed significant increases in documentation (p < 0.05). In all 3 questions asked to healthcare professionals, fewer healthcare professionals were required to revisit archived notes following proforma implementation (p < 0.05). CONCLUSION: Our study illustrates that a comprehensive surgical clerking proforma improves patient data documentation and saves healthcare professionals' time compared to the freehand clerking method. The implications of such work are far reaching, and if well implemented could allow a new reliable platform for further clinical audits.

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

BACKGROUND: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study.

BACKGROUND: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. METHODS: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score--GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. RESULTS: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 × 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P(interaction) = 0.014), CADM2 rs13078960 (P(interaction) = 0.037) and GALNT10 rs7715256 (P(interaction) = 0.048) with physical activity, and PTBP2 rs11165643 (P(interaction) = 0.045), HIP1 rs1167827 (P(interaction) = 0.015), C6orf106 rs205262 (P(interaction) = 0.032) and GRID1 rs7899106 (P(interaction) = 0.043) with smoking on BMI. CONCLUSIONS: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.

Mild Cognitive Impairment in Rural Tanzania: Prevalence, Profile, and Outcomes at 4-Year Follow-up.

OBJECTIVE: Mild cognitive impairment (MCI) is recognized as a high-risk condition for conversion to dementia, although data on outcomes of MCI in sub-Saharan Africa are scarce. We investigated outcomes of MCI over a 4-year period in Tanzania and considered risk factors for conversion to dementia. METHODS: In a longitudinal cohort study in the Hai district, Tanzania, patients with MCI were identified during a two-phase prevalence study carried out in 2010. Of 1,198 people aged 70 years and over screened in phase I, a stratified sample of 296 were fully assessed in phase II. MCI was defined according to international consensus criteria. DSM-IV criteria were used for dementia diagnosis. Background demographic and risk factor data were collected, and neuropsychiatric symptoms were assessed using the neuropsychiatric inventory. Patients were followed-up in 2011, 2012 and 2014. RESULTS: Forty-six MCI patients were identified. After adjusting for stratification, the crude prevalence of MCI was 7.0% (95% CI: 3.6-10.4). Over a 4-year period, 15 patients (32.6%) progressed to dementia, 2 patients (4.3%) returned to normal cognition, 1 developed late-onset schizophrenia, 8 patients (17.4%) had stable MCI, 19 patients (41.3%) died, and 1 refused assessment. Age, sex, education levels, body mass index, hypertension, and comorbidity were not associated with progression to dementia. CONCLUSION: In this rural Tanzanian population, rates of conversion from MCI to DSM-IV dementia were similar to those reported in high-income countries. Over a third of all patients had died at the 4-year follow-up.

Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

BACKGROUND: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population. METHODS: The Karachi Intracranial Stenosis Study is a case-control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations. CONCLUSIONS: ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

Palliative care in people with idiopathic Parkinson's disease who die in hospital.

BACKGROUND: The UK National Institute for Health and Clinical Excellence guidelines state that palliative care options for people with Parkinson's disease (PD) should be discussed. AIMS: To investigate whether palliative care guidelines are adhered to for people with PD who die in hospital. SETTING/PARTICIPANTS: The medical notes of all people with a diagnosis of idiopathic PD who were living in two adjacent areas of northeast England and who died over a 3-year period were examined. Demographic data and specific information regarding events around the time of death were recorded. RESULTS: For the 236 patients identified, the average age at death was 82.8 years. Of these patients, 110 (46.6%) died in hospital, 56 (23.7%) at home, 59 (25.0%) in a care home and for 11 patients (4.7%) the place of death was not recorded. For those who died in hospital, only three patients, and seven relatives of patients, had had a recorded discussion with a clinician regarding their preferred place of death and only 15 (13.6%) were referred to a specialist palliative care team. Forty-six patients (41.8%) were placed on the Liverpool Care Pathway. CONCLUSIONS: For those dying in hospital, there are few previously documented end-of-life care discussions with patients or their relatives. The use of end-of-life pathways and access to specialist palliative care is variable. Following the Neuberger report, the Liverpool Care Pathway is to be replaced with individual end-of-life care plans. It is important to engage patients, and their relatives, in decision making regarding preferences at the end of life.

Development and Validation of the Identification and Intervention for Dementia in Elderly Africans (IDEA) Study Dementia Screening Instrument.

AIM: The aim of this project was to develop a dementia screening instrument for use in the hospital or community in populations with low levels of formal education. METHODS: A screening instrument was developed from retrospective data collected in a rural area of Tanzania in 2010. The community screening instrument for dementia was administered to over 95% of the population aged 70 years and older of 6 villages (n = 1198) in Hai district, Tanzania. Factor analysis, regression modeling, and Mokken scale analysis (MSA) were used to develop screening instruments from these data, which were then tested and refined during prospective fieldwork. RESULTS: A 5-item screening instrument with an area under the receiver-operating characteristic (AUROC) curve of 0.871, sensitivity of 91.7%, and specificity of 61.7% was developed using a combination of factor analysis and logistic regression modeling and had a higher AUROC (0.786) than a 7-item screening instrument developed using MSA. During prospective testing and refinement (n = 60), the 5-item instrument performed well (AUROC 0.867) and took an average of less than 10 minutes to administer. Its performance was improved by including a matchstick design item added to measure praxis, AUROC 0.888. CONCLUSIONS: The 6-item brief dementia screening instrument has acceptable properties and will be further tested and validated during future fieldwork. Although developed for use in sub-Saharan Africa, it may be of use in other world regions where the use of other cognitive screening instruments may result in bias due to low levels of formal education.

Hypercalcemia in a male-to-female transgender patient after body contouring injections: a case report.

INTRODUCTION: Body contouring injections by non-licensed providers are frequently sought out by a subset of the male-to-female transgender community. Although short-term side effects such as pulmonary embolism and injection site infection are well known, long-term consequences of such practices are less well studied. CASE PRESENTATION: Here we describe the case of a 40-year-old African American male-to-female transgender patient who presented to our institution with hypercalcemia and acute renal failure secondary to body contouring injections with industrial strength silicone by non-licensed providers, a decade prior to her visit. Work-up revealed an extensive granulomatous inflammatory process in the injection area resulting in electrolyte abnormalities and kidney injury. The patient's lab results and symptoms responded well to long-term corticosteroid treatment and correlated with treatment adherence. CONCLUSION: Affected patients can sometimes present with unusual clinical symptoms many years after silicone injections. In a constantly growing transgender community that often utilizes non-licensed providers for silicone injections, the medical community will likely face an increasing number of patients with long-term side effects of such practices. Therefore, it is imperative for physicians to recognize such cases promptly and initiate potentially life-saving treatment.

Stroke radiology and distinguishing characteristics of intracranial atherosclerotic disease in native South Asian Pakistanis.

BACKGROUND: There are no descriptions of stroke mechanisms from intracranial atherosclerotic disease in native South Asian Pakistanis. METHODS: Men and women aged ≥ 18 years with acute stroke presenting to four tertiary care hospitals in Karachi, Pakistan were screened using magnetic resonance angiography/transcranial Doppler scans. Trial of ORG 10172 in Acute Stroke Treatment criteria were applied to identify strokes from intracranial atherosclerotic disease. RESULTS: We studied 245 patients with acute stroke due to intracranial atherosclerotic disease. Two hundred thirty scans were reviewed. Also, 206/230 (89.0%) showed acute ischaemia. The most frequent presentation was with cortically based strokes in 42.2% (87/206) followed by border-zone infarcts (52/206, 25.2%). Increasing degrees of stenosis correlated with the development of both cortical and border-zone strokes (P = 0.002). Important associated findings were frequent atrophy (166/230, 72.2%), silent brain infarcts (66/230, 28%) and a marked lack of severe leukoaraiosis identified in only 68/230 (29.6%). A total of 1870 arteries were studied individually. Middle cerebral artery was the symptomatic stroke vessel in half, presenting with complete occlusion in 66%. Evidence of biological disease, symptomatic or asymptomatic was identified in 753 (40.2%) vessels of which 543 (72%) were significantly (>50%) stenosed at presentation. CONCLUSION: Intracranial atherosclerotic disease is a diffuse process in Pakistani south Asians, with involvement of multiple vessels in addition to the symptomatic vessel. The middle cerebral artery is the most frequent symptomatic vessel presenting with cortical embolic infarcts. There is a relative lack of leukoaraiosis. Concomitant atrophy, silent brain infarcts and recent ischaemia in the symptomatic territory are all frequently associated findings.

Russell body duodenitis: a histopathological and molecular approach to a rare clinical entity.

Russell bodies are pink eosinophilic accumulations within plasma cells. To date, two hypotheses have attempted to elucidate the biological events behind the formation of these bodies. One theory sustains that such bodies constitute cytoplasmic accumulation of immunoglobulin derivatives contained in the perinuclear cistern of the smooth endoplasmic reticulum because of an increased synthesis or altered secretion. On the other hand, since its initial description in the medical literature, several authors have attributed the formation of such bodies to the presence of microorganisms such as in the case of Russell body gastritis and its association to Helicobacter pylori infection. In an attempt to possibly characterize the presence of an infectious organism, we performed a thorough biomolecular analysis on a case of a 69-year-old female presenting with Russell body duodenitis which, to the best of our knowledge, constitutes the second report of this clinical entity in the English literature. In light that the events behind formation of such bodies in H. pylori-negative individuals remain unclear, we hypothesize on the possible pathways that could have led to their reactive mechanical and immune derivation.

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.

Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

BACKGROUND: Evidence is sparse about the genetic determinants of major lipids in Pakistanis. METHODS AND RESULTS: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). CONCLUSIONS: Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.

OBJECTIVE: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. METHODS AND RESULTS: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis. CONCLUSIONS: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

The Karachi intracranial stenosis study (KISS) Protocol: an urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan.

BACKGROUND: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner. METHODS/DESIGN: The Karachi Intracranial Stenosis Study (KISS) is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due to intracranial stenosis and compare them to those with stroke due to other etiologies as well as to unaffected individuals. We plan to recruit 200 patients with stroke due to intracranial stenosis and two control groups each of 150 matched individuals. The first set of controls will include patients with ischemic stroke that is due to other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes. The second group will consist of stroke free individuals. Standardized interviews will be conducted to determine demographic, medical, social, and behavioral variables along with baseline medications. Mandatory procedures for inclusion in the study are clinical confirmation of stroke by a healthcare professional within 72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition, lipid profile, serum glucose, creatinine and HbA1C will be measured in all participants. Ancillary tests will include carotid ultrasound, transcranial doppler and magnetic resonance or computed tomography angiogram to rule out concurrent carotid disease. Echocardiogram and other additional investigations will be performed at these centers at the discretion of the regional physicians. DISCUSSION: The results of this study will help inform locally relevant clinical guidelines and effective public health and individual interventions.

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.