Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

Changing the paradigm in postherpetic neuralgia treatment: lidocaine 700 mg medicated plaster.

OBJECTIVE: Chronic pain is currently considered a disease state with biopsychosocial consequences and a negative impact on patients' quality of life (QoL). Pain from postherpetic neuralgia (PHN) can persist for months or years and is a prototypical example of chronic pain. We analyzed PHN as a model of chronic pain, including its effects on QoL and clinical aspects. We explored treatment options, focusing on the topical treatment with lidocaine 700 mg medicated plaster (LMP) and how this impacts PHN management. MATERIALS AND METHODS: This article is a narrative review of published studies. Preclinical and clinical studies were retrieved from literature through a search performed in PubMed/MEDLINE. RESULTS: To choose the appropriate treatment for chronic pains, such as PHN, not only efficacy but also tolerability, manageability, practicality, and compliance are important factors, especially in the long term. It is also important to set treatment expectations with the patients as total suppression of pain may be unrealistic, and a balance needs to be found between pain control and the minimization of adverse events. In this respect, LMP may be the best currently available treatment: it is easy to use, has low systemic absorption and thus a low risk for pharmacological interactions. Therefore, treatments can be personalized, and concomitant medications can be added, if needed. Recent data from a real-world study support this view by showing that LMP has superior effectiveness in reducing pain and improving the QoL compared to other commonly used systemic treatments and confirming its good tolerability profile that is mainly characterized by localized skin reactions. CONCLUSIONS: LMP is one of the best currently available treatment options for PHN patients balancing good efficacy with an excellent tolerability profile and can therefore be considered for use as a first-line treatment for PHN.

El problema no resuelto del dolor postoperatorio: análisis crítico y propuestas de mejora / The unsolved problem of postoperative pain: critical analysis and prospects for improvement

Anualmente se ha observado un ascenso del 5 % en la intervenciones quirúrgicas realizadas mundialmente, junto con un incremento en la complejidad de las mismas, así como en la comorbilidades de los pacientes. No obstante, entre el 30-80 % de los pacientes experimentan dolor agudo postoperatorio (DAP) mode­rado-intenso tras las primeras 24 horas de postoperatorio, a pesar de un mejor conocimiento fisiopatológico, el empleo de nuevas técnicas y fármacos analgésicos, la publicación de nuevas guías y la creación de las Unidades de Dolor Agudo (UDA). Además, hemos de tener presente a los pacientes vulnerables (población pediátrica, gestantes, ancianos, etc.) y a los consumidores crónicos de opioides, que habitualmente son desviaciones de los protocolos analgésicos y, por tanto, nos sitúan en un escenario en el que el manejo del dolor postoperatorio es más difícil y obliga al diseño de estrategias personalizadas a cada paciente. Se ha de tener también presente que un inadecuado control del DAP puede dar lugar a una cronificación del dolor postoperatorio, suponiendo un auténtico reto te­rapéutico para las unidades de dolor crónico, junto con un deterioro de la calidad de vida del paciente debido a sus repercusiones físicas, psicológicas y económicas. A través de este manuscrito, pretendemos realizar un análisis crítico y proponer puntos de mejora en la forma en la que gestionamos actualmente el DAP, basándonos en la evidencia científica para la obtención de mejores resultados postoperatorios en los próximos años.(AU)

Annually, a 5 % rise has been observed in surgical interventions performed worldwide, together with an increase in their complexity as well as in patient comorbidities. However, between 30-80 % of patients experience moderate-intense acute postoperative pain (APD) after the first 24 postoperative hours, despite better pathophysiological knowledge, use of new techniques and analgesic drugs, publication of new guidelines and the creation of the Acute Pain Units (UDA). In addition, we must bear in mind vulnerable patients (pediatric population, pregnant women, the elderly, ...) and chronic opioid users who are usually deviations from analgesic protocols and, therefore, place us in a scenario in which the management of Postoperative pain is more difficult and requires the design of personalized strategies for each patient. It must also be borne in mind that inadequate PDA control can lead to chronic postoperative pain, posing a real therapeutic challenge for Chronic Pain Units, toge­ther with a deterioration in the patient's quality of life due to its physical repercussions, psychological and economic. Through this manuscript, we intend to carry out a critical analysis and propose points for improvement in the way we currently manage DAP based on scientific evidence to obtain better postoperative results in the coming years.(AU)

Patient and caregiver reported facilitators of self-care among patients with chronic heart failure: report from a formative qualitative study.

Background: Adherence to a complex, yet effective medication regimen improves clinical outcomes in patients with chronic heart failure (CHF). However, patient adherence to an agreed upon plan for medication-taking is sub-optimal and continues to hover at 50% in developed countries. Studies to improve medication-taking have focused on interventions to improve adherence to guideline-directed medication therapy, yet few of these studies have integrated patients' perceptions of what constitutes effective strategies for improved medication-taking and self-care in everyday life. The purpose of this formative study was to explore patient perceived facilitators of selfcare and medication-taking. Methods: We conducted in-depth interviews of patients with long standing heart failure admitted to the cardiology and internal medicine wards of a South Indian tertiary care hospital. We purposively sampled using the following criteria: sex, socio-economic status, health literacy and patient reported medication adherence in the month prior to hospitalization. We employed inductive coding to identify facilitators. At the end of 15 interviews (eight patients and seven caregivers; seven patient-caregiver dyads), we arrived at theoretical saturation for facilitators. Results: Facilitators could be classified into intrinsic (patient traits - situational awareness, self-efficacy, gratitude, resilience, spiritual invocation and support seeking behavior) and extrinsic (shaped by the environment - financial security and caregiver support, company of children, ease of healthcare access, trust in provider/hospital, supportive environment and recognizing the importance of knowledge). Conclusions: We identified and classified a set of key patient and caregiver reported self-care facilitators among Indian CHF patients. The learnings from this study will be incorporated into an intervention package to improve patient engagement, overall self-care and patient-caregiver-provider dynamics.

Using an amplitude analysis to measure the photon polarisation in B → K π π γ decays.

A method is proposed to measure the photon polarisation parameter λ γ in b → s γ transitions using an amplitude analysis of B → K π π γ decays. Simplified models of the K π π system are used to simulate B + → K + π - π + γ and B 0 → K + π - π 0 γ decays, validate the amplitude analysis method, and demonstrate the feasibility of a measurement of the λ γ parameter irrespective of the model parameters. Similar sensitivities to λ γ are obtained with both the charged and neutral hadronic systems. In the absence of any background and distortion due to experimental effects, the statistical uncertainty expected from an analysis of B + → K + π - π + γ decays in an LHCb data set corresponding to an integrated luminosity of 9  fb - 1 is estimated to be 0.009. A similar measurement using B 0 → K + π - π 0 γ decays in a Belle II data sample corresponding to an integrated luminosity of 5  ab - 1 would lead to a statistical uncertainty of 0.018.

Características de los corticoides particulados y no particulados. Condicionantes para su uso en el tratamiento del dolor crónico / Characteristics of particulate and non-particulate corticosteroids. Indications for their use in chronic pain treatments

El uso de corticoides en el tratamiento del dolor ha sido una práctica habitual desde mediados del siglo pasado. A raíz de una revisión de las complicaciones acontecidas con su administración por vía epidural, la Administración de Alimentos y Medicamentos de Estados Unidos (FDA) emitió una «controvertida alerta» solicitando se añada una «advertencia» en el etiquetado de los corticoides inyectables donde se deben describir dichos riesgos (pérdida de la visión, derrame cerebral, parálisis y muerte) al ser suministrados por esta vía. Es importante resaltar la existencia de diferentes clases de corticoides con características diversas que hace, que los potenciales efectos secundarios de su uso también sean distintos. Creemos necesario, en vista de los acontecimientos mencionados, las controversias que se han generado y la falta de estudios bien realizados sobre el uso de los corticoides, tanto en infiltraciones epidurales y como en otros procedimientos, comenzar por realizar una revisión general sobre sus indicaciones, efectos secundarios, complicaciones y características particulares de los diferentes compuestos en diversas enfermedades dolorosas (AU9

Corticosteroids been used frequently in pain treatments since the middle of last century (1952). Due to a review of the complications as a result of their application in epidural injections, the United States of America Food and Drug Administration (FDA) issued an «alert controversy» requesting that a warning label should be added to injectable corticosteroids, where risks must be described (loss of sight, brain damage, paralysis and death) when administering by this route. It must be mentioned that there are different types of corticosteroids with diverse characteristics, which as a result, may produce different side-effects. Due to the aforementioned developments, the controversies that have arisen, and the lack of well-conducted studies on the use of steroids in epidural injections, we must begin by reviewing their indications in different pain conditions (AU)

Characteristics of particulate and non-particulate corticosteroids. Indications for their use in chronic pain treatments. / Características de los corticoides particulados y no particulados. Condicionantes para su uso en el tratamiento del dolor crónico.

Corticosteroids been used frequently in pain treatments since the middle of last century (1952). Due to a review of the complications as a result of their application in epidural injections, the United States of America Food and Drug Administration (FDA) issued an «alert controversy¼ requesting that a warning label should be added to injectable corticosteroids, where risks must be described (loss of sight, brain damage, paralysis and death) when administering by this route. It must be mentioned that there are different types of corticosteroids with diverse characteristics, which as a result, may produce different side-effects. Due to the aforementioned developments, the controversies that have arisen, and the lack of well-conducted studies on the use of steroids in epidural injections, we must begin by reviewing their indications in different pain conditions.

Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics

AbstractBACKGROUND:Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS:A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS:Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS:The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

Prevalence, risk factors and awareness of hypertension in India: a systematic review.

Indians have high rates of cardiovascular disease. Hypertension (HTN) is an important modifiable risk factor. There are no comprehensive reviews or a nationally representative study of the burden, treatments and outcomes of HTN in India. A systematic review was conducted to study the trends in prevalence, risk factors and awareness of HTN in India. We searched MEDLINE from January 1969 to July 2011 using prespecified medical subject heading (MeSH) terms. Of 3372 studies, 206 were included for data extraction and 174 were observational studies. Prevalence was reported in 48 studies with sample size varying from 206 to 167 331. A significant positive trend (P<0.0001) was observed over time in prevalence of HTN by region and gender. Awareness and control of HTN (11 studies) ranged from 20 to 54% and 7.5 to 25%, respectively. Increasing age, body mass index, smoking, diabetes and extra salt intake were common risk factors. In conclusion, from this systematic review, we record an increasing trend in prevalence of HTN in India by region and gender. The awareness of HTN in India is low with suboptimal control rates. There are few long-term studies to assess outcomes. Good quality long-term studies will help to understand HTN better and implement effective prevention and management programs.

Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial.

BACKGROUND: The combination of three blood-pressure-lowering drugs at low doses, with a statin, aspirin, and folic acid (the polypill), could reduce cardiovascular events by more than 80% in healthy individuals. We examined the effect of the Polycap on blood pressure, lipids, heart rate, and urinary thromboxane B2, and assessed its tolerability. METHODS: In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged 45-80 years, and with one risk factor were randomly assigned, by a central secure website, to the Polycap (n=412) consisting of low doses of thiazide (12.5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other groups, each with about 200 individuals, of aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering drugs, three blood-pressure-lowering drugs alone, or three blood-pressure-lowering drugs plus aspirin. The primary outcomes were LDL for the effect of lipids, blood pressure for antihypertensive drugs, heart rate for the effects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, and rates of discontinuation of drugs for safety. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00443794. FINDINGS: Compared with groups not receiving blood-pressure-lowering drugs, the Polycap reduced systolic blood pressure by 7.4 mm Hg (95% CI 6.1-8.1) and diastolic blood pressure by 5.6 mm Hg (4.7-6.4), which was similar when three blood-pressure-lowering drugs were used, with or without aspirin. Reductions in blood pressure increased with the number of drugs used (2.2/1.3 mm Hg with one drug, 4.7/3.6 mm Hg with two drugs, and 6.3/4.5 mm Hg with three drugs). Polycap reduced LDL cholesterol by 0.70 mmol/L (95% CI 0.62-0.78), which was less than that with simvastatin alone (0.83 mmol/L, 0.72-0.93; p=0.04); both reductions were greater than for groups without simvastatin (p<0.0001). The reductions in heart rate with Polycap and other groups using atenolol were similar (7.0 beats per min), and both were significantly greater than that in groups without atenolol (p<0.0001). The reductions in 11-dehydrothromboxane B2 were similar with the Polycap (283.1 ng/mmol creatinine, 95% CI 229.1-337.0) compared with the three blood-pressure-lowering drugs plus aspirin (350.0 ng/mmol creatinine, 294.6-404.0), and aspirin alone (348.8 ng/mmol creatinine, 277.6-419.9) compared with groups without aspirin. Tolerability of the Polycap was similar to that of other treatments, with no evidence of increasing intolerability with increasing number of active components in one pill. INTERPRETATION: This Polycap formulation could be conveniently used to reduce multiple risk factors and cardiovascular risk.

Melioidosis.

Melioidosis is an emerging infectious disease in India acquired through percutaneous inoculation or contaminated water. Known risk factors include diabetes mellitus, renal failure, cirrhosis, and malignancy. Melioidosis presents with a febrile illness, with protean manifestations ranging from septicemia to localized abscess formation. We present the case of a 42-year-old male from a non-endemic region who presented with fever of 2 months duration, sepsis, persistent pneumonia, right hip joint pain and hepatic and splenic abscesses. Aspiration of the joint and soft tissue fluid collection and subsequent culture yielded gram negative bacilli identified as Burkholderia pseudomallei. The epidemiology, clinical features, and laboratory diagnosis of this rare infection and its treatment is reviewed.

Impacto asistencial de las técnicas oncoplásticas conservadoras en un programa quirúrgico para enfermas con cáncer de mama / Impact of conservative oncoplastic techniques in a surgery program for women with breast cancer

Objetivos. Evaluar el impacto asistencial de las técnicas oncoplásticas conservadoras en un programa quirúrgico de mujeres con cáncer de mama. Pacientes y método. El grupo a estudio lo constituyeron enfermas sometidas a una técnica oncoplástica conservadora mientras que el grupo control lo formaron mujeres intervenidas con técnicas conservadoras (tumorectomía/cuadrantectomía) y radicales (mastectomía). Los criterios de inclusión para una técnica oncoplástica comprendieron mujeres con tumores de diámetro inferior a 3 cm, tumores T2 tratados con quimioterapia neoadyuvante y reducidos a un tamaño menor de 3 cm, en estadios clínicos axilares N0-N1a-b y procesos multifocales (infiltrante y/o in situ). Se excluyó del estudio a las mujeres con tumores T3-4, imposibilidad para la radioterapia postoperatoria, volumen mamario reducido e imposibilidad de márgenes libres de enfermedad durante el estudio intraoperatorio. Resultados. Durante el período se intervino a 160 mujeres en las que se practicaron 50 técnicas oncoplásticas (29 para evitar una mastectomía y 21 para mejorar el resultado de la técnica conservadora), 57 técnicas conservadoras y 53 mastectomías. Las técnicas utilizadas para la remodelación mamaria fueron la mamoplastia horizontal (23 casos), la mamoplastia vertical de pedículo superior (10 casos), la mamoplastia vertical de pedículo inferior (10 casos), la mamoplastia de rotación (4 casos) y la mamoplastia lateral (3 casos). El grupo de técnicas oncoplásticas presentó un tiempo medio de intervención (131 min) superior a las técnicas conservadoras (56 min) y radicales (93 min). La incidencia de complicaciones postoperatorias fue mayor en las técnicas radicales (35%), fundamentalmente por seromas axilares tras linfadenectomía, respecto a las técnicas conservadoras (25%) y oncoplásticas (24%). Conclusiones. Las técnicas oncoplásticas constituyen una alternativa eficaz y eficiente a las técnicas quirúrgicas convencionales en la mujer con cáncer de mama (AU)

Objectives. To evaluate the impact of conservative oncoplastic techniques in a surgery program for women with breast cancer. Patients and method. The study group was composed of women who underwent a conservative oncoplastic technique and the control group consisted of women who underwent conservative (tumorectomy/quadrantectomy) and radical (mastectomy) techniques. Women with tumors smaller than 3 cm, axillary clinical stages N0-N1a-b and multifocal processes (infiltrating and/or in situ) were eligible for inclusion. Women with T3-4 tumors and reduced breast volume, and those in whom postoperative radiotherapy and disease-free margins during intraoperative study were not feasible were excluded. Results. One hundred sixty women underwent surgery during the study period. Fifty oncoplastic techniques (29 to avoid mastectomy and 21 to improve the result of a conservative technique), 57 conservative techniques and 53 mastectomies were performed. The techniques used for breast reconstruction were superior mammoplasty with transversal scar (23 patients), mammoplasty with superior pedicle (10 patients), mammoplasty with inferior pedicle (10 patients), J-shapped mammoplasty (four patients) and oblique mammoplasty (three patients). The mean operating time in the group undergoing oncoplastic techniques (131 minutes) was higher than that in the group undergoing conservative (56 minutes) and radical (93 minutes) techniques. The incidence of postoperative complications was higher with radical techniques (35%), mainly due to axillary seromas after lymphadenectomy, than with conservative (25%) and oncoplastic (24%) techniques. Conclusions. Oncoplastic techniques are an effective and efficient alternative to conventional surgical techniques in women with breast cancer (AU)

[Impact of conservative oncoplastic techniques in a surgery program for women with breast cancer]. / Impacto asistencial de las técnicas oncoplásticas conservadoras en un programa quirúrgico para enfermas con cáncer de mama.

OBJECTIVES: To evaluate the impact of conservative oncoplastic techniques in a surgery program for women with breast cancer. PATIENTS AND METHOD: The study group was composed of women who underwent a conservative oncoplastic technique and the control group consisted of women who underwent conservative (tumorectomy/quadrantectomy) and radical (mastectomy) techniques. Women with tumors smaller than 3 cm, axillary clinical stages N0-N1a-b and multifocal processes (infiltrating and/or in situ) were eligible for inclusion. Women with T3-4 tumors and reduced breast volume, and those in whom postoperative radiotherapy and disease-free margins during intraoperative study were not feasible were excluded. RESULTS: One hundred sixty women underwent surgery during the study period. Fifty oncoplastic techniques (29 to avoid mastectomy and 21 to improve the result of a conservative technique), 57 conservative techniques and 53 mastectomies were performed. The techniques used for breast reconstruction were superior mammoplasty with transversal scar (23 patients), mammoplasty with superior pedicle (10 patients), mammoplasty with inferior pedicle (10 patients), J-shapped mammoplasty (four patients) and oblique mammoplasty (three patients). The mean operating time in the group undergoing oncoplastic techniques (131 minutes) was higher than that in the group undergoing conservative (56 minutes) and radical (93 minutes) techniques. The incidence of postoperative complications was higher with radical techniques (35%), mainly due to axillary seromas after lymphadenectomy, than with conservative (25%) and oncoplastic (24%) techniques. CONCLUSIONS: Oncoplastic techniques are an effective and efficient alternative to conventional surgical techniques in women with breast cancer.

Pre hospital issues in acute myocardial infarction.

OBJECTIVES: Time is of prime importance in the management of acute myocardial infarction (AMI). Time to hospital admission should be minimised for maximum thrombolytic benefit. The present paper has evaluated some socio-demographic factors influencing pre hospital delay. METHODS: This prospective observational study of 1,072 patients with AMI admitted to 14 hospitals in South India was done over one year. Socio-demographic factors viz. time of symptom onset, place of residence, type of transportation to hospital, distance travelled, as well as clinical and treatment details were recorded. Hospitals were grouped based on their location into metropolitan and town hospitals. RESULTS: Males predominated (85%) and had AMI at a younger age than females. Most patients (74%) travelled less than 30 km to a hospital. The mean distance travelled to a town hospital was longer than that to a metropolitan hospital (24.2 km vs 21 km; p < 0.0001); however there was no significant difference in the type of transportation or time taken to reach either of the hospitals. Majority (79%) of patients arrived at a hospital within the thrombolytic window of 12 hours (mean time = 11 hours). The occurrence of a previous MI had no influence on time taken to hospital arrival, questioning the role of symptom education as an interventional strategy to reduce pre hospital delay. Patients older than 70 years and females in towns with symptom onset during the day (6 am to 6 pm) took a longer time to reach hospital. CONCLUSION: Community facilities do not affect pre hospital delay. Interventions should focus on reducing decision time to call for help and the role of symptom education needs further evaluation.

Increased risk of acute myocardial infarction associated with beedi and cigarette smoking in Indians: final report on tobacco risks from a case-control study.

BACKGROUND: Tobacco smoking is an important risk factor for ischemic heart disease. In India, tobacco is smoked both as cigarettes and beedies. No studies have evaluated their importance as risk factors for ischemic heart disease among the Indian population. The present study explores the importance of smoking either cigarettes or beedies as risk factors for acute myocardial infarction. METHODS AND RESULTS: The study had a case-control design and was conducted in a tertiary teaching hospital in Bangalore. Three hundred subjects aged 30-60 years with a first acute myocardial infarction and 300 age- and sex-matched controls were recruited prospectively. Smoking, dietary and social history were recorded, body mass index and waist-hip ratio measured, and blood glucose, lipids, fasting plasma and insulin levels estimated. Cases and controls had a mean age of 47.2 years and 46.8 years, respectively. There were 279 (93%) males in each group. Diabetes mellitus (odds ratio 2.69, p<0.0009). hypertension (odds ratio 2.36, p=0.0009), fasting and post-load blood glucose (p<0.0001). and waist-hip ratio (p<0.0001) were found to be important risk factors for acute myocardial infarction. Smoking was an independent risk factor with a clear dose effect. Adjusted odds ratio for smoking > or = 10 cigarettes/day was 3.58 (p<0.0001) and was 4.36 (p<0.0001) for smoking > or = 10 beedies/day. CONCLUSIONS: Smoking > or = 10 cigarettes or beedies/day carries an independent four-fold increased risk of acute myocardial infarction. This reiterates the need for urgent tobacco control measures in India.

Chromatographic and related techniques for the determination of aromatic heterocyclic amines in foods.

Some 20 years ago, Japanese scientists discovered a new group of highly toxic compounds, classified as heterocyclic aromatic amines, from broiled and grilled meat and fish products. Numerous studies have shown that most HAs are mutagenic and carcinogenic, and the safety of HA-containing foods has become a concern for the public. To date, more than 20 different mutagenic and/or carcinogenic heterocyclic amines have been identified in foods. This paper reviews the analysis of foods for HAs with 145 references. We survey some of the numerous methods available for the chromatographic analysis of heterocyclic amines and highlight the recent advances. We discuss chromatographic and related techniques, including capillary electrophoresis, and their coupling to mass spectrometry for the determination of these contaminants in foods. In addition, the review summarises data on the content of HAs in various cooked foods.

Formation of the mutagen IFP in model systems and detection in restaurant meats.

Mixtures of the free amino acids, creatine and glucose, were dry-heated to model the potential formation of heterocyclic amines in meats. The formation of the mutagenic amine IFP (determined to be 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine) was investigated by varying heating time, heating temperature, and precursors. With an optimized mixture of glutamine, creatine, and glucose, heated at 200 degrees C for 60 min, 2 mg of IFP was purified for studies to define its structure. Trideuteriomethyl-IFP was made from trideuteriomethylcreatinine in the model system for use in LC-MS detection of IFP in foods. Analysis of well-done meats purchased from restaurants showed about half to contain IFP at levels from 1.4 to 46 ng/g of cooked meat, demonstrating human exposure to this mutagen.