Patient safety in India

The recent Editorial in The National Medical journal of India, discussed about the patient safety in India. The hospitals are now busy places with so many patients undergoing many different treatments and tests. It is very essential that all the precautions are taken in to account to avoid the problems or complications. It is important to realize that hospitals and members of the profession are held accountable for the short falls in care.The 1995 Supreme Court declaration bringing hospitals under the purview of the Consumers Protection Act (CPA) of 1986 was possibly the start of the movement for the safety of the patient in India. The WHO launched the World Alliance on Patient Safety (WAPS) to help stimulate further research to ascertain the extent and root causes of the problem and, more importantly, develop innovative solutions to reduce the burden of harm due to unsafe healthcare. Much progress has since been made, in the past decade, but it is equally clear from some high-profile instances, for example, in the National Health Service (NHS) in the UK that a lot more needs to be done (http://www.midstaffsinquiry.com/). India is a signatory to the WAPS and institutions such as the Quality Council of India have been set up. There are also other initiatives, such as the National Initiative on Patient Safety at the All India Institute of Medical Sciences and the Indian Confederation for Healthcare Accreditation, to promote action. We need to build on these developments. We could start with a five-pronged approach.
1. Lobbying and assisting institutions and the government with the creation of systems for recording, learning and reporting on the quality of services and adverse events in a ‘balanced’ manner (neither too heavy-handed, nor too light), and making it possible to set up such systems given the concerns of such documentation.
2. Accelerating the implementation of proven patient safety interventions, such as the Global Patient Safety Challenges work on hand hygiene and surgical checklist, andTHE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 25, NO. 3, 2012 131 by the introduction of mandatory compliance with ‘Never Events’ (http://www.telegraph.co.uk/health/healthnews/4933949/List-of-eight-blunders-the-NHSmust-never-commit-released-by-watchdog.html).
3. Empowering patients to question and work with professionals, for example through the Patient Safety Alliance (www.patientsafetyalliance.in), which also draws on the work being done by the Health Education Library for Patients (www.healthlibrary.com).
4. Capacity-building through education and training at the undergraduate level by using the WHO curriculum on patient safety and for established professionals through distance learning, for example through the  people’s Open Access Education Initiative (www.peoples-uni.org).
5. Undertaking further research by building on the work started by the INCLEN.

So, patient safety is clearly a major public health issue in India, and some would argue that the problem is likely to be much more serious, given the concerns about counterfeit drugs, faulty medical equipment, unsafe blood banks or unregulated organ donation, for example. There is lot of work to do in the coming years in this direction!!!

Missing early diagnosis of Diabetes!

It is generally felt that the diagnosis is often missed or delayed in remote areas where the medical facilities are not available and medical insurance facilities are not able to reach. In India, it is common to see medical camps being conducted in the rural areas to detect the non communicable diseases such as diabetes and hypertension. In some countries even though there are all the medical facilities available the diagnosis of diabetes is often delayed due to many reasons. Limited access to health care, especially being uninsured and going without insurance for a long period, was significantly associated with being a “missed patient” with diabetes. Efforts to increase detection of diabetes may need to address issues of access to care. In the coming years more and more attention will be given to the non communicable diseases and we can reduce the number of undetected diabetes people and improve their health care through the insurance systems.
Reference: Diabetes Care. 2008 September; 31(9): 1748–1753.

Vitamian K antagonists (OACs) are harmful?

 Can we safeguard coronaries from micro calcification?

As Weijs et al.^[1] have described, most patients diagnosed with paroxysmal atrium fibrillation (AF) are currently treated by prescribing life-long use of vtamin K antagonists (VKAs) to prevent thrombo-embolic complications.[2] By applying minimal invasive multislice computed tomography (MSCT) imaging, the authors found a possible adverse treatment effect in patients who were receiving VKAs for relatively longer, showing significant higher levels of calcium in their coronary arteries compared with patients with a shorter time on VKAs. This could have serious consequences for current clinical practice.[2]

 1. Weijs B, Blaauw Y, Rennenberg RJMW, Schurgers LJ et al. Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J 2011;32:2555-2562. First published on 20 July 2011. doi:10.1093/eurheartj/ehr226. 

2. Fuster V, Ryden LE,Cannom DS,Crijns HJ et al.. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J 2006;27:1979-2030.

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Lower extremities amputaitons are decreasing!

Amputations can be prevented -  amputation rates are decreasing!!!
It is important to know that the methods to reduce amputation and improve the quality of life are measurably effective in some countries such as America. During the last 25 years of our service at our institution in Hyderabad, the amputation rate has come down, but still the patients are coming for advice very late. That means we need to encourage the govt hospital doctors at primary care centers to recognize these problems early and treat the risk factors before they are unmanageable. That is the best way to control the epidemic cardiovascular diseases. Bypasses and balloon angioplasties will help to some extent but the larger populations can be benefited by the identification and modification of the risk factors. It may be worth developing risk modification clinics across the state to address this issue and improve the quality of life. The Aarogyasree scheme is very helpful to the people but it is going to be better if they also spend money for the development of the risk modification clinics.


Temporal Trends and Geographic Variation of Lower-Extremity Amputation in Patients With Peripheral Artery DiseaseResults From U.S. Medicare 2000–2008
W. Schuyler Jones, MD; Manesh R. Patel, MD; David Dai, PhD; Sumeet Subherwal, MD, MBA; Judith Stafford, MS; Sarah Calhoun, BS; Eric D. Peterson, MD, MPH
J Am Coll Cardiol. 2012;60(21):2230-2236. doi:10.1016/j.jacc.2012.08.983
Abstract
Objectives This study sought to characterize temporal trends, patient-specific factors, and geographic variation associated with amputation in patients with lower-extremity peripheral artery disease (LE PAD) during the study period.
Background Amputation represents the end-stage failure for those with LE PAD, and little is known about the rates and geographic variation in the use of LE amputation.
Methods By using data from the Centers for Medicare & Medicaid Services (CMS) from January 1, 2000, to December 31, 2008, we examined national patterns of LE amputation among patients age 65 years or more with PAD. Multivariable logistic regression was used to adjust regional results for other patient demographic and clinical factors.
Results Among 2,730,742 older patients with identified PAD, the overall rate of LE amputation decreased from 7,258 per 100,000 patients with PAD to 5,790 per 100,000 (p < 0.001 for trend). Male sex, black race, diabetes mellitus, and renal disease were all independent predictors of LE amputation. The adjusted odds ratio of LE amputation per year between 2000 and 2008 was 0.95 (95% CI: 0.95–0.95, p < 0.001).
Conclusions From 2000 to 2008, LE amputation rates decreased significantly among patients with PAD. However, there remains significant patient and geographic variation in amputation rates across the United States.

Obesity and deep vein thrombosis

Obesity and Deep vein thrombosis

Obesity is measured as body mass index above 30. The body mass index (BMI) is measured as weight in kilograms divided by the square of height in meter. Obesity is associated with venous thromboembolism (VTE). Body mass index is a marker of excess weight and correlates well with body fat content in adults. Body mass index fails to consider the importance of the distribution of body fat. All measurements of obesity are predictors of the risk for VTE. Positive associations were found between VTE and body weight, body mass index, waist circumference, hip circumference, and total body fat mass (1). The fact is that the fat distribution is not uniform in all the people and so there are different shapes of individuals. Basically obesity is differentiated as central or peripheral depending on the degree of fat accumulation in the central part of the body or extremities. Studies were done to find out the differences in risk associated with these types of fat distribution. The distribution of body fat predicts the risk of arterial thrombotic events, such as coronary heart disease (CHD). Central obesity is a better predictor of CHD than general obesity as measured with BMI.  Central obesity is measured as waist circumference or waist-to-hip ratio. It is important note that peripheral obesity is not a predictor of coronary heart disease. The peripheral obesity is measured as hip circumference (2,3). One study evaluated the association between VTE and central obesity in men and found that a waist circumference >100 cm was associated with a higher risk of VTE than a waist circumference  less than 100 cm (4).It is also important know the benefit of thrombo-prophylaxis in obese people who are undergoing major surgeries such as total knee arthroplasty. In a case-control study, they studied (130, 463) patient with and patients without acute VTE (within 9 days of surgery) and BMI ranging from 17 to 61.  Multivariable logistic regression was used to analyze risk factors for postoperative VTE, adjusted for age and gender. Thromboprophylaxis was LMWH in 284 (48%), warfarin in 189 (32%), both in 55 (10%), and mechanical prophylaxis alone in 120 (20%). Overall, 77% ambulated on day 1 or 2 after surgery. Severe obesity was not a significant independent predictor for VTE and did not modify the beneficial effect of FDA-approved pharmacological thromboprophylaxis. Bilateral TKA and failure to ambulate by the second day after surgery were significant risk factors (5). 

References:

1.   Knut H. Borch, Sigrid K. Brækkan, Ellisiv B. Mathiesen, Inger Njølstad, Tom Wilsgaard, Jan Størmer, and John-Bjarne Hansen. Anthropometric Measures of Obesity and Risk of Venous Thromboembolism: The Tromsø Study. Arterioscler Thromb Vasc Biol. 2010;30:121-12.   

2.   Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, Buchan I, Day N, Khaw KT. Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007; 116: 2933–2943. 

3.   Yang L, Kuper H, Weiderpass E. Anthropometric characteristics as predictors of coronary heart disease in women. J Intern Med. 2008; 264: 39–49 

4.   Hansson PO, Eriksson H, Welin L, Svardsudd K, Wilhelmsen L. Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913.” Arch Intern Med. 1999; 159: 1886–1890.

5.   Sadeghi B, Romano PS, Maynard G, Strater AL, Hensley L, Cerese J, White RH. Mechanical and suboptimal pharmacologic prophylaxis and delayed mobilization but not morbid obesity are associated with venous thromboembolism after total knee arthroplasty: A case-control study. J Hosp Med. 2012 Oct 5. doi: 10.1002/jhm.1962. [Epub ahead of print]

Blood goups and risk of proximal DVT

What is your blood group? if you have  O+  blood group, then you are probably safer than Non-O blood group people !!!

Non-O blood group in people seems to influence the risk of deep vein thrombosis.  In a study on 712 DVT patients, significant thrombotic risk was noted in those with Non O blood group and thrombophilia. In such patients the risk for DVT can be almost 3-fold higher.

Blood Transfus. 2012 Oct 11:1-5. doi: 10.2450/2012.0060-12. [Epub ahead of print]
ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia.
Spiezia L, Campello E, Bon M, Tison T, Milan M, Simioni P, Prandoni P.
Although having a non-O blood type is now regarded as a risk factor for venous thromboembolism, the strength of this association is poorly defined, as is its interaction with inherited thrombophilia.
MATERIALS AND METHODS:The prevalence of non-O blood group and inherited thrombophilia (deficiencies of natural anticoagulants, factor V Leiden and prothrombin G20210A mutation) was assessed in a series of 712 consecutive patients with proximal deep vein thrombosis (DVT) of the lower limbs who were referred to our Institution between 2004 and 2010, and in 712 age- and gender-matched healthy volunteers. Odds ratios (OR) of DVT and their 95% confidence intervals (CI) were computed for non-O group and thrombophilia, both separately and in combination.
RESULTS:A non-O blood group was present in 492 cases and 358 controls (OR 2.21; 95% CI, 1.78 to 2.75). A thrombophilic abnormality was present in 237 cases and 105 controls (OR 2.82; 2.18 to 3.66). The combination of non-O group and thrombophilia was present in 152 cases and 51 controls (OR 7.06; 4.85 to 10.28).
DISCUSSION:Having a non-O blood group is associated with an increased risk of proximal DVT of the lower limbs with or without pulmonary embolism. The addition of inherited thrombophilia increases the thrombotic risk conferred by non-O group alone by almost 3-fold.

Why we are not preventing Diabetes?

Diabetes mellitus is going to affect the health of millions if it is allowed to continue to raise in the present manner and we are aware of this noncommunicable disease epidemic. There are some measures to delay the onset or prevent the diabetes mellitus. It is going to be essential to findout why these measures are not adequately implemented in the countries. There studies to find out the reasons for the indequate preventive measure implementation.

The Diabetes Prevention Program (DPP) clinical trial and its 10-year outcomes study (DPPOS), both sponsored by the National Institutes of Health (NIH), showed that certain interventions could prevent or substantially delay the onset of type 2 diabetes both safely and cost-effectively. Yet diabetes prevention is not widely practiced in the United States, and the disease's staggering human and financial costs continue to grow. It is therefore essential to identify the factors impeding the full realization of the DPP interventions' potential for preventing diabetes.

In DPP trial (3234) overweight or obese adults with IGT (prediabetes) were assigned to receive one of three interventions: lifestyle intervention aimed at modest weight loss through diet and exercise, treatment with generic metformin, or a placebo control. DPP findings published in 2002 indicated that, relative to placebo, lifestyle intervention and metformin reduced the rate of conversion to diabetes by 58% and 31%, respectively, over 3 years.1

Metformin worked well in younger women with history of gestational diabetes. Exercise and life style modifications worked well in people ( both genders) above 60 years of age.

Most DPP participants (88%) enrolled in the DPPOS ( 10 year study) , in which continued follow-up demonstrated that the 10-year risk reduction for type 2 diabetes was 31% for lifestyle intervention and 18% for metformin.2

We need to wait and see in India for the effectiveness of life style modifications in the rural and urban populations in preventing IGT conversion to diabetes mellitus, this can avert major risks associated with the potential epidemic of diabetes in the coming years.

18F-Fludeoxyglucose PET/CT in the evaluation of large-vessel vasculitis

British Journal of Radiology (2012) 85, e188-e194 

¹⁸F-Fludeoxyglucose PET/CT in the evaluation of large-vessel vasculitis: diagnostic performance and correlation with clinical and laboratory parameters  N D Papathanasiou Correspondence: Dr Jamshed Bomanji, Institute of Nuclear Medicine, University College Hospital, 235 Euston Road, London NW1 2BU, UK. E-mail: jamshed.bomanji@uclh.nhs.uk

Abstract

Objective: To investigate the diagnostic performance of ¹⁸F-fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT in patients with suspected large-vessel vasculitis and its potential to evaluate the extent and activity of disease.

Methods: 78 consecutive patients (mean age 63 years; 53 females) with suspected large-vessel vasculitis were evaluated with ¹⁸F-FDG PET/CT. ¹⁸F-FDG uptake in the aorta and major branches was visually graded using a four-point scale and quantified with standardised uptake values (SUV_max). According to clinical diagnosis, patients were classified into three groups: (a) steroid-naïve, large-vessel vasculitis (16 patients), (b) vasculitis on steroid treatment (18 patients) and (c) no evidence of vasculitis (44 patients). Analysis of variance and linear regression were used to investigate the association of ¹⁸F-FDG uptake with clinical diagnosis and inflammatory markers.

Results: ¹⁸F-FDG PET/CT was positive (visual uptake ≥2; equal to or greater than liver) in all patients with steroid-naïve, large-vessel vasculitis. The thoracic aorta, the carotid and the subclavian arteries were most frequently involved. 

Conclusion: ¹⁸F-FDG PET/CT can detect the extent and activity of large-vessel vasculitis in untreated patients and is unreliable in diagnosing vasculitis in patients on steroids.

Metallo Beta lactamase producing pseudomonas aeruginosa and its association with diabetic foot.

Diabetic foot infections are common and there is increasing possibility that they are getting resistant to all antibiotics available due to inadequate or inappropriate use of them. Infection with multi drug resistance organisms (MDROs) is common in diabetic foot ulcers and is associated with inadequate glycemic control and increased requirement for surgical treatment.

Pseudomonas aeruginosa strains that produce metallo beta lactamases (MBLs) are becoming increasingly prevalent in wound infections

Indian J Surg. 2011 Aug;73(4):291-4. Epub 2011 May 3.

Residents vs attending surgeons

Coronary Artery Bypass Graft Patency: Residents Versus Attending Surgeons

Faisal G. Bakaeen, MD, Gulshan Sethi, MD, Todd H. Wagner, PhD,
Rosemary Kelly, MD, Kelvin Lee, PhD, Anjali Upadhyay, MS, Hoang Thai, MD,
Elizabeth Juneman, MD, Steven Goldman, MD, and William L. Holman, MD
Michael E. DeBakey Veterans Affairs Medical Center and Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Division of Cardiovascular Surgery, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas; Department of Cardiothoracic Surgery, University of Arizona Health Science Center, Tucson, Arizona; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Department of Cardiovascular Surgery, University
of Minnesota Hospital, Minneapolis, Minnesota; Southern Arizona Veterans Affairs Health Care System and University of Arizona, Tucson, Arizona; and Division of Cardiothoracic Surgery, University of Alabama, Birmingham, Alabama 

Background. Data are limited regarding the patency of coronary artery bypass grafts performed by residents versus attending surgeons.
 

Methods. We analyzed data from a multicenter, randomized Veterans Affairs Cooperative Study in which the left internal mammary artery was used preferentially to graft the left anterior descending coronary artery, and the best remaining coronary vessel received (per random assignment) either a radial artery or a saphenous vein graft. The study vessel’s 1-year graft patency was the primary outcome measure. Secondary outcomes included operative times, operative morbidity, mortality, repeat revascularization, cost, angina symptoms, and quality of life. Multivariate analyses were used to compare patient outcomes for residents versus attendings. 

Results. Residents were designated as primary surgeons in 23% of cases (167 of 725). Among the 531 patients who had a 1-year angiogram, study graft patency rates for resident cases (n 122) and attending cases (n 409) were not significantly different (86% versus 90%, p 0.22). Residents’ cases had longer perfusion time (119 versus 105 minutes, p < 0.0001) and cross-clamp time (84 versus 68 minutes, p < 0.0001). After risk adjustment, all outcome measures did not differ between the two groups, and there was no apparent interaction effect between resident/ attending designation and radial artery versus saphenous
vein use or on-pump versus off-pump approach.

Conclusions. Surgeons in training perform coronary artery bypass surgery without compromising graft patency or patient outcomes. Ongoing evaluation of residents’ performance and surgical outcomes is needed, given the major changes that are occurring in residency training.

(Ann Thorac Surg 2012;94:482– 8) © 2012 by The Society of Thoracic Surgeons

Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease.

J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76.

West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, Berr SS, Harthun NL, Weltman AL, Dimaria JM, Hunter JR, Christopher JM, Kramer CM.

Source

Department of Medicine, University of Virginia Health System, University of Virginia, Charlottesville, Virginia.

Abstract

OBJECTIVES:

We hypothesized that low-density lipoprotein (LDL) reduction regardless of mechanism would improve calf muscle perfusion, energetics, or walking performance in peripheral arterial disease (PAD) as measured by magnetic resonance imaging and magnetic resonance spectroscopy.

BACKGROUND:

Statins improve cardiovascular outcome in PAD, and some studies suggest improved walking performance.

METHODS:

Sixty-eight patients with mild to moderate symptomatic PAD (age 65 ± 11 years; ankle-brachial index [ABI] 0.69 ± 0.14) were studied at baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naïve, or ezetimibe 10 mg (n = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P magnetic resonance spectroscopy immediately after symptom-limited calf exercise on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast-enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise. Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were performed. A repeated-measures model compared changes over time.

RESULTS:

LDL reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe 10 mg group (116 ± 42 mg/dl to 56 ± 21 mg/dl) than in the simvastatin 40 mg group (129 ± 40 mg/dl to 90 ± 30 mg/dl, p < 0.01). LDL also decreased in the ezetimibe 10 mg group (102 ± 28 mg/dl to 79 ± 27 mg/dl, p < 0.01). Despite this, there was no difference in perfusion, metabolism, or exercise parameters between groups or over time. Resting ABI did improve over time in the ezetimibe 10 mg group and the entire study group of patients.

CONCLUSIONS:

Despite effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor exercise parameters improved, although rest ABI did. Thus, LDL lowering does not improve calf muscle physiology or functional capacity in PAD. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

Statins and Peripheral Arterial Disease

Based on the Heart Protection Study, persons with PAD should be treated with statins regardless of age, gender, or initial serum lipids levels. 

In addition to that  - Three double-blind, randomized, placebo-controlled studies have also demonstrated that statins improve walking performance in persons with PAD.

In a study of 69 persons, mean age 75 years, with intermittent claudication, a mean ABI of 0.63, and a serum LDL cholesterol of 125 mg/dl or higher, 3 of 34 persons (9%) treated with simvastatin and 6 of 35 persons (17%) treated with placebo died before the 1-year study was completed . Compared with placebo, simvastatin significantly increased treadmill exercise time until the onset of intermittent claudication by 24% at 6 months and by 42% at 1 year after therapy. 

In a study of 354 persons, mean age 68 years, with intermittent claudication and hypercholesterolemia, at 1-year follow-up, compared with placebo, atorvastatin 80 mg daily significantly improved pain-free treadmill walking distance by 40% and significantly improved community-based physical activity. 

In a study of 86 persons, mean age 67 years, with intermittent claudication and hypercholesterolemia, at 6-month follow-up, compared with placebo, simvastatin 40 mg daily significantly improved pain-free walking distance and total walking distance on a treadmill, significantly improved the mean ABI at rest and after exercise, and significantly improved symptoms of claudication.

It is also interesting to note that Statin use is also associated with superior leg functioning independent of cholesterol levels and other potential confounders. The data suggest that non-cholesterol-lowering properties of statins may influence functioning in persons with and without PAD.

1. Aronow WS, Nayak D, Woodworth S, Ahn C. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at 6 months and at 1 year after treatment. Am J Cardiol. 2003;92:711–2. 

2. Mohler ER, III, Hiatt WR, Creager MA., the Study Investigators Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108:1481–6.

3. Mondillo S, Ballo P, Barbati R, et al. Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med. 2003;114:359–64.

Lancet. 2002 Jul 6;360(9326):7-22. 

MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.

Heart Protection Study Collaborative Group.

Abstract  : Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations.

METHODS: 20,536 UK adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85%) or matching placebo (average non-study statin use: 17%). Analyses are of the first occurrence of particular events, and compare all simvastatin-allocated versus all placebo-allocated participants. These "intention-to-treat" comparisons assess the effects of about two-thirds (85% minus 17%) taking a statin during the scheduled 5-year treatment period, which yielded an average difference in LDL cholesterol of 1.0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin daily). Primary outcomes were mortality (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity.

FINDINGS: All-cause mortality was significantly reduced (1328 [12.9%] deaths among 10,269 allocated simvastatin versus 1507 [14.7%] among 10,267 allocated placebo; p=0.0003), due to a highly significant 18% (SE 5) proportional reduction in the coronary death rate (587 [5.7%] vs 707 [6.9%]; p=0.0005), a marginally significant reduction in other vascular deaths (194 [1.9%] vs 230 [2.2%]; p=0.07), and a non-significant reduction in non-vascular deaths (547 [5.3%] vs 570 [5.6%]; p=0.4).  

The proportional reduction in the event rate was similar (and significant) in each subcategory of participant studied, including: those without diagnosed coronary disease who had cerebrovascular disease, or had peripheral artery disease, or had diabetes; men and, separately, women; those aged either under or over 70 years at entry; and--most notably--even those who presented with LDL cholesterol below 3.0 mmol/L (116 mg/dL), or total cholesterol below 5.0 mmol/L (193 mg/dL). The benefits of simvastatin were additional to those of other cardioprotective treatments. The annual excess risk of myopathy with this regimen was about 0.01%. There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause.

 

INTERPRETATION: Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients, irrespective of their initial cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rates of myocardial infarction, of stroke, and of revascularisation by about one-quarter. After making allowance for non-compliance, actual use of this regimen would probably reduce these rates by about one-third. Hence, among the many types of high-risk individual studied, 5 years of simvastatin would prevent about 70-100 people per 1000 from suffering at least one of these major vascular events (and longer treatment should produce further benefit). The size of the 5-year benefit depends chiefly on such individuals' overall risk of major vascular events, rather than on their blood lipid concentrations alone.

Vascular malformations in the forearm subcutaneous tissues can be completely excised. This video shows the excision of the Lymphovenous malformation on the lateral aspect of the upper and middle 1/3rd of the forearm in the cephalic vein zone.