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.

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.

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.

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.

[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.

Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings.

Mixtures of amino acids, creatine, and glucose simulating the composition of six different kinds of meats (beef, chicken breast, chicken thigh, turkey breast, pork, and fish) were dry-heated to simulate the formation of heterocyclic amines in meats. The presence of 16 heterocyclic amines was investigated in the model systems and in the six meats and their corresponding meat drippings to determine the importance of meat composition to heterocyclic amine formation. Nine mutagenic amines (IQ, MeIQ, 8-MeIQx, 4,8-DiMeIQx, PhIP, IQx, IFP, DMIP, and TMIP) were found to be present at concentrations >0.1 ng/g in some of the model systems and in some of the meats or pan residues. Heterocyclic amine concentrations clearly are affected by precursor composition in this model system, and the same nine heterocyclic amines formed in the meat and in the model system show that this is a well-controlled surrogate for the reaction conditions that occur in meats during cooking.

Treatment of acute myocardial infarction: does the type of hospital make a difference? PPAMI Study Group.

There is sparse data on the treatment practices being followed for acute myocardial infarction at various hospitals that differ in their financial infrastructure, availability of facilities and attachment to a medical college. In this prospective observational study, we evaluated the treatment practices for acute myocardial infarction, its appropriateness based on ACC/AHA guidelines and possible influence by type of hospital and certain patient characteristics. Thrombolysis, beta-blockers and angiotensin-converting enzyme-I inhibitors were used in 674 (63%), 506 (47%) and 413 (38%) respectively of 1072 patients. However, when evaluated according to ACC/AHA guidelines, appropriate use was noted in 83 percent, 78 percent and 99.3 percent, respectively. Thrombolysis was inappropriately denied to 14.7 percent patients whereas in 2.4 percent it was used contrary to recommendations. The most common reason for ineligibility for thrombolysis was late arrival. Beta-blockers were denied to 25.1 percent patients. Decision on use of angiotensin-converting enzyme-I was appropriate in most patients. Aspirin was used in 1027 (95.8%) patients. Government hospitals were least likely to thrombolyse a patient as compared to private, industrial and voluntary hospitals; however, this difference was not seen with the use of beta-blockers and angiotensin-converting enzyme-I. Hospitals attached to medical colleges follow guidelines for use of thrombolysis and beta-blockers more closely than non-teaching hospitals. To conclude, evaluation of appropriateness of a therapeutic modality is of greater clinical significance than mere absolute use. Benefits of thrombolytic therapy can be extended by minimising pre-hospital delay; and there is scope for improved utility of beta-blockers which are cost-effective. In addition, the hospital type also has an impact on the treatment practice being followed for acute myocardial infarction.