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Worldwide, major depression is the leading cause of years lived with a disability, and the fourth cause of disability-adjusted life years. Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Unfortunately, despite the high prevalence of depression, under-recognition and under-treatment are common.Historically, clinicians have assessed the short-term effectiveness of antidepressants by response rates, often defined as a 50% reduction in depressive symptoms. However, this usually does not reflect true clinical remission, and residual symptoms are common. Persistence of residual symptoms appears to be a common link to relapse, chronic disability and suicide. The burden of not treating depression effectively to remission is significant, as the disease is an important contributor to the disability levels of the general population. Disability, in turn, has a profound impact on lost productivity and medical expenses. In 2000, depression cost the US more than US 83 billion dollars annually in lost productivity, medical expenses and premature death.Venlafaxine, a dual-acting serotonin norepinephrine (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment and their chances of achieving complete remission compared with conventional antidepressant therapies, with the evidence for this being the strongest for comparisons with the selective serotonin receptor inhibitors (SSRIs). To date, there are only a small number of economic studies of venlafaxine, and most are cost or resource utilisation analyses with significant limitations. Nevertheless, two cost-effectiveness analyses of venlafaxine are available. They found venlafaxine had a lower average cost per patient achieving remission or per symptom-free day compared with SSRIs; one reported an incremental cost-effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per additional patient achieving remission over 8 weeks, and the other found venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001 values). Although requiring further confirmation, these initial data suggest that venlafaxine is a cost-effective strategy for the treatment of depression. The availability of an effective armamentarium of antidepressant strategies, including venlafaxine, to achieve and sustain remission offers both clinical and economic value to all those touched by the burden of depression.
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PMID:Remission from depression : a review of venlafaxine clinical and economic evidence. 1596 May 53

The Swiss Organ Living Donor Health Registry (SOL-DHR) started in April 1993. The purpose was the prospective and sequential follow up of donors long-term health. Between 1993 and January 2005 737 Living Kidney donations were registered and followed. Two thirds of donors were female and two thirds of recipients male. The three most common relations were life-partners, parents and siblings (approximately 30% each). 10% of donors could not be followed since living far abroad and 5% were lost due to missing current address after moving. 9 donors died (4 malignancies, 2 traffic accidents, 1 myocardial infarction, 1 stroke and 1 suicide), non due to kidney donation. Perioperative complications were age dependent, ranging from 17% in donors below the age of 40 year and 46% in donors older than 70 years. The longterm complications were divided in surgical, medical and psychological ones. The most common surgical long-term complications were pain (cicatrice, back, abdomen) and hernias. The major medical complications were hypertension (35% at seven years after donation) and rising rate of Albuminuria (9% at seven years). Although hypertension was not higher than in an age matched Swiss control population, untreated hypertension was regarded as the higher risk for development of glomerulosclerosis than in people with two kidneys. No donor went into end stage renal failure. Using the SF-8-Test to quantify the psychological well-being the mean MCS (mental component summary) was 54.3 +/- 7.8 as compared to 52.9 +/- 7.7 in the age matched control population. MCS was low (< 40) in 6.2% and very low (< 25) in 2.2% of donors. 94.4 % of donors would donate again, while 4.3% would not (mostly women). The reasons not to donate again was mainly related to poor outcome of the kidney recipient, or long-lasting major pain or disappointment about medical handling before (not enough information, wrong advice) and after organ donation. The association of Swiss Living Organ Donors, where only kidney or liver donors can become a member, are organising self-help-groups for pain, psychological and financial problems (with health insurances). The organisation and financial support of SOL-DHR is briefly described. The waste majority of living kidney donors are very satisfied about the free care given by SOL-DHR.
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PMID:[The Swiss Organ Living Donor Health Registry (SOL-DHR)]. 1607 50

Pregnancy-related death is defined by the International Classification of Diseases, Tenth Revision (ICD-10) as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death. In the year 2000, a collaborative effort involving World Health Organization (WHO), UNICEF, and UNFPA estimated 660 maternal deaths in the United States. This averages 11 maternal deaths per 100,000 live births reported. Many pregnancy-associated deaths are not easily identified as such since the presence of a recent or current pregnancy may not be listed on the death certificate. Thus, the WHO estimates that in the United States, the maternal mortality is approximately 17/100,000 pregnancies. This is significantly higher than the goal set by the US Department of Health and Human Services in Healthy People 2010, which sets the target for maternal mortality at less than 3.3/100,000 live births. The most common causes of maternal death vary somewhat from region to region in the United States. They include pulmonary thromboembolism, amniotic fluid embolism, primary postpartum uterine hemorrhage, infection, and complications of hypertension including preeclampsia and eclampsia. Pulmonary disease, complications of anesthesia, and cardiomyopathy also are significant contributors to maternal mortality in some populations. The death of a pregnant or recently pregnant individual poses a wide scope of challenges to the forensic pathologist and investigator. The pathologist must have a broad knowledge of the physiologic and biochemical changes that occur during pregnancy, as well as the clinical and pathological manifestation of these changes. Conditions that may be "benign" in the nonpregnant individual may be lethal in the puerperal period. In addition, it should be kept in mind that deaths during pregnancy may be due to unnatural causes. Accident, homicide, and suicide must be ruled out in each case. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina from January 1989 through December 2003. All decedents listed as pregnant or postpartum were analyzed as to maternal age, race, past medical history, previous pregnancies and outcome, prenatal care, gestational age, fetal or neonatal outcome, location of delivery, placental findings, maternal autopsy findings, toxicology, cause of death, manner of death, and fetal or neonatal autopsy findings. The authors present this retrospective study to better determine the factors leading to maternal demise and discuss the autopsy/ancillary techniques useful in determining the cause of death in this challenging area.
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PMID:Pregnancy-associated deaths: a 15-year retrospective study and overall review of maternal pathophysiology. 1650 42

Isotretinoin (13-cis-retinoic acid) is a retinoid that is used to treat cystic acne, comedonal acne, and other diseases. For the treatment of acne, isotretinoin is dosed at 0.5 to 2 mg/kg daily for 5 months with a target total dose of approximately 120 mg/kg. Its most common side effects are mucocutaneous and ocular in nature (ie, cheilitis, ocular sicca, and decreased dark adaptation). It can also cause xerosis. Patients should be made aware of these side effects before taking isotretinoin and also that utilization of moisturizers and eye drops can help to mitigate such side effects. Sometimes, however, the dose of isotretinoin needs to be decreased to reduce the induction of side effects. Isotretinoin's most significant side effect is the induction of birth defects if a fetus is exposed to isotretinoin, which is pregnancy category X. Isotretinoin should be used with 2 forms of birth control by fecund women. It can rarely increase serum levels of triglycerides, which can, if very elevated, be related to the development of pancreatitis and xanthomas. Isotretinoin's well-documented but rarer side effects include intracranial hypertension. It can induce bony changes. A review of the literature demonstrates that isotretinoin is not linked to depression and suicide. Facial swelling has been linked to isotretinoin use in 3 previous case reports. We note herein the first case of facial swelling that occurred in an acne patient being treated with isotretinoin who at the time the swelling developed had no cysts, comedones, pustules, or evidence of bacterial infection. Possible reasons for the patient's facial swelling include some type of retinoid induced angioedema, exacerbation of inflammation by isotretinoin, and isotretinoin induced capillary leak syndrome.
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PMID:Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin. 1670 87

Unhealthy alcohol use is among the leading causes of morbidity and mortality in the United States. Among military personnel, service members between the ages 18 and 25 had a 27.3% prevalence of heavy drinking in the previous 30 days, compared to 15.3% among civilians in the same age group. In the civilian world, > 100 million patients are treated in U.S. emergency departments (ED) annually; 7.9% of these visits are alcohol related. Alcohol is associated with a broad range of health consequences that may ultimately present in the ED setting: traumatic injuries (e.g., motor vehicle crashes, intentional violence, falls); environmental injuries (e.g., frostbite); cardiovascular problems (e.g., hypertension, dilated cardiomyopathy); gastrointestinal disorders (e.g., hepatitis, pancreatitis, gastrointestinal bleeding); neurological problems (e.g., encephalopathy, alcohol withdrawal, withdrawal seizures), as well as psychological problems (e.g., depression, suicide). Seminal work has been done to create behavioral interventions for at-risk drinkers. These motivational interventions have been found to be successful in encouraging clients to change their risky behaviors. We present such a technique, called the Brief Negotiated Interview as performed in a civilian ED setting, in hopes of adapting it for use in the military context. Military health care providers could easily adapt this technique to help reduce risky levels of alcohol consumption among service members, retirees, or military dependents.
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PMID:Brief interventions to reduce harmful alcohol use among military personnel: lessons learned from the civilian experience. 1680 38

A few epidemiologic studies have shown an increased risk of death from external causes among men with hypertension. Previous studies were limited by small numbers of events, however, and none assessed the association of blood pressure with specific types of "accidental" death. The authors examined data obtained from baseline interviews and 25 years of mortality follow-up (1973-1999) for 347,978 men screened for the US Multiple Risk Factor Intervention Trial. Proportional hazards regression analyses were used to quantify associations of blood pressure with all external causes of death and individual causes. There were 3,910 deaths from external causes, including 2,313 unintentional injuries, 1,248 suicides, and 349 homicides. Compared with those for men whose blood pressure status was "normal" according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, the multivariate-adjusted hazard ratios and 95% confidence intervals for death from external causes among men with prehypertension, stage 1 hypertension, and stage 2 hypertension were 0.91 (95% confidence interval (CI): 0.83, 1.00), 1.06 (95% CI: 0.96, 1.16), and 1.44 (95% CI: 1.28, 1.62), respectively. Men with stage 2 hypertension had multivariate-adjusted hazard ratios of 1.90 for falls (95% CI: 1.32, 2.74), 1.45 for motor vehicle injuries (95% CI: 1.14, 1.85), 1.33 for other "accidents" (95% CI: 1.06, 1.66), 1.40 for suicide (95% CI: 1.13, 1.73), and 1.35 for homicide (95% CI: 0.92, 1.97). For men, hypertension may signal an increased risk of death from external causes.
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PMID:Blood pressure and risk of death from external causes among men screened for the Multiple Risk Factor Intervention Trial. 1709 20

Cardiovascular disease (CVD), which includes coronary heart, cerebrovascular, and peripheral vascular disease, is the leading cause of death in the United States and most developed countries, accounting for about 50% of all deaths. The major risk factors include obesity and its consequences, dyslipidemia, hypertension, insulin resistance leading to diabetes, and cigarette smoking. In developing countries, CVD will become the leading cause of death due to alarming increases in obesity, sedentary lifestyles, cigarette smoking, and improvements in prevention and treatment of malnutrition and infection. Compared with nonschizophrenics, patients with schizophrenia have a 20% shorter life expectancy (i.e., from 76 to 61 years). In general populations, about 1% die from suicide compared with about 10% among patients with schizophrenia (relative risk = 10). For CVD, the corresponding figures are 50% and about 75% (relative risk = 1.5). In patients with schizophrenia, however, CVD occurs more frequently and accounts for more premature deaths than suicide. Patients with schizophrenia have alarmingly higher rates of obesity, dyslipidemia, hypertension, diabetes, and cigarette smoking than nonschizophrenic individuals in the general population. Compounding these data, patients with schizophrenia have less access to medical care, consume less medical care, and are less compliant. Primary prevention strategies should include the choice of antipsychotic drug regimens that do not adversely affect the major risk factors for CVD.
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PMID:Increasing global burden of cardiovascular disease in general populations and patients with schizophrenia. 1753 93

Rgs2 (regulator of G-protein signaling-2)-deficient mice exhibit severe hypertension, and genetic variations of RGS2 occur in hypertensive patients. RGS2 mRNA up-regulation by angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) is a potentially important negative feedback mechanism in blood pressure homeostasis, but how it occurs is unknown. Here we demonstrate that group VIA phospholipase A2 (iPLA2beta) plays a pivotal role in Ang II-induced RGS2 mRNA up-regulation in VSMC by three independent approaches, including pharmacologic inhibition with a bromoenol lactone suicide substrate, suppression of iPLA2beta expression with antisense oligonucleotides, and genetic deletion in iPLA2beta-null mice. Selective inhibition of iPLA2beta by each of these approaches abolishes Ang II-induced RGS2 mRNA up-regulation. Furthermore, using adenovirus-mediated gene transfer, we demonstrate that restoration of iPLA2beta-expression in iPLA2beta-null VSMC reconstitutes the ability of Ang II to up-regulate RGS2 mRNA expression. In contrast, Ang II-induced vasodilator-stimulated phosphoprotein phosphorylation and Ang II receptor expression are unaffected. Moreover, in wild-type but not iPLA2beta-null VSMC, Ang II stimulates iPLA2 enzymatic activity significantly. Both arachidonic acid and lysophosphatidylcholine, products of iPLA2beta action, induce RGS2 mRNA up-regulation. Inhibition of lipoxygenases, particularly 15-lipoxygenase, and cyclooxygenases, but not cytochrome P450-dependent epoxygenases inhibits Ang II- or AA-induced RGS2 mRNA expression. Moreover, RGS2 protein expression is also up-regulated by Ang II, and this is attenuated by bromoenol lactone. Disruption of the Ang II/iPLA2beta/RGS2 feedback pathway in iPLA2beta-null cells potentiates Ang II-induced vasodilator-stimulated phosphoprotein and Akt phosphorylation in a time-dependent manner. Collectively, our results demonstrate that iPLA2beta participates in Ang II-induced transcriptional up-regulation of RGS2 in VSMC.
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PMID:Group VIA phospholipase A2 (iPLA2beta) participates in angiotensin II-induced transcriptional up-regulation of regulator of g-protein signaling-2 in vascular smooth muscle cells. 1761 34

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascular disease (CVD) and reduced life expectancy, over and above that imposed by their mental illness through suicide. Several levels of evidence from data linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metabolic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.
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PMID:Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia. 1765 24

Schizophrenia is a life-threatening disease associated with mortality rates that are two to three times higher than those expected/observed in the general population. It is associated with high levels of suicide, particularly in young male patients soon after diagnosis. Delays in treating schizophrenia could contribute to the high number of suicides during this period. However, approximately two-thirds of the excess mortality is caused by natural deaths. Patients with schizophrenia die from the same diseases as people in the general population. The number of deaths caused by cardiovascular disease, as in the general population, is high and could be reduced by the modification of certain lifestyle factors, such as diet and exercise. Careful monitoring of patients' weight, blood pressure, blood glucose levels and serum lipid levels will not only provide an opportunity to educate patients about lifestyle choices that contribute to cardiovascular disease but will also give them a better chance of receiving early treatment for disorders that contribute to cardiovascular disease, such as obesity, type 2 diabetes, hypertension and dyslipidaemia. Careful selection of antipsychotic drugs, some of which are associated with side effects such as weight gain and cardiac disorders, will also help reduce co-morbidity and mortality among patients with schizophrenia.
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PMID:Mortality in schizophrenia. 1794


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