Potential causes of higher mortality in elderly users of conventional and atypical antipsychotic medications

OBJECTIVES: To investigate the potential mechanisms through which conventional antipsychotic medication (APM) might act, the specific causes of death in elderly patients newly started on conventional APM were compared with those of patients taking atypical APM. DESIGN: Cohort study. SETTING: Community. PARTICIPANTS: All British Columbia residents aged 65 and older who initiated a conventional or atypical APM between 1996 and 2004. MEASUREMENTS: Cox proportional hazards models were used to compare risks of developing a specific cause of death within 180 days of APM initiation. Potential confounders were adjusted for using traditional multivariable, propensity‐score, and instrumental‐variable adjustments. RESULTS: The study cohort included 12,882 initiators of conventional APM and 24,359 initiators of atypical APM. Of 3,821 total deaths within the first 180 day of use, cardiovascular (CV) deaths accounted for 49% of deaths. Initiators of conventional APM had a significantly higher adjusted risk of all CV death (hazard ratio (HR)=1.23, 95% confidence interval (CI)=1.10–1.36) and out‐of‐hospital CV death (HR=1.36, 95% CI=1.19–1.56) than initiators of atypical APM. Initiators of conventional APM also had a higher risk of death due to respiratory diseases, nervous system diseases, and other causes. CONCLUSION: These data suggest that greater risk of CV deaths might explain approximately half of the excess mortality in initiators of conventional APM. The risk of death due to respiratory causes was also significantly higher in conventional APM use.     

Weight loss in overweight patients maintained on atypical antipsychotic agents

BACKGROUND: Weight gain and associated medical morbidity offset the reduction of extrapyramidal side effects associated with atypical antipsychotics. Efforts to control weight in antipsychotic-treated patients have yielded limited success. METHODS: We studied the impact of an intensive 24-week program of diet, exercise, and counseling in 17 chronically psychotic patients (10 women, seven men) who entered at high average body weight (105.0+/-18.4 kg) and body mass index (BMI) (36.6+/-4.6 kg/m(2)). A total of 12 subjects who completed the initial 24 weeks elected to participate in an additional 24-week, less intensive extension phase. RESULTS: By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11% improvement), pulse fell slightly, and serum cholesterol and triglyceride concentrations changed nonsignificantly. With less intensive management for another 24 weeks, subjects regained minimal weight (0.43 kg). CONCLUSIONS: These findings add to the emerging view that weight gain is a major health problem associated with modern antipsychotic drugs and that labor-intensive weight-control efforts in patients requiring antipsychotic treatment yield clinically promising benefits. Improved treatments without weight-gain risk are needed.     

Abnormalities in glucose metabolism in patients with schizophrenia treated with atypical antipsychotic medications

The incidence of carbohydrate intolerance and overt diabetes is increased in patients with schizophrenia treated with the newer atypical antipsychotic agents. The precise mechanism for these abnormalities remains obscure. This review examines the potential interaction between atypical antipsychotic medications and several hormones known to influence appetite regulation and carbohydrate metabolism.     

Venous thromboembolism in patients hospitalized with nephrotic syndrome

Purpose

Whether pulmonary embolism in patients with the nephrotic syndrome is caused by deep venous thrombosis or renal vein thrombosis is controversial. To determine which is the likely cause of pulmonary embolism in patients with the nephrotic syndrome, we investigated data from the National Hospital Discharge Survey.

Methods

The number of patients discharged from nonfederal short-stay hospitals in the United States with a diagnostic code of nephrotic syndrome, deep venous thrombosis, renal vein thrombosis, and pulmonary embolism was obtained using ICD-9-M (International Classification of Diseases, Ninth Revision, Clinical Modification) codes.

Results

From 1979 to 2005, 925,000 patients were discharged from hospitals with the nephrotic syndrome and 898,253,000 patients did not have the nephrotic syndrome. With the nephrotic syndrome, 5000 (0.5%) had pulmonary embolism, 14,000 (1.5%) had deep venous thrombosis, and fewer than 5000 had renal vein thrombosis. The relative risk of pulmonary embolism comparing patients with the nephrotic syndrome to those who did not have it was 1.39, and the relative risk of deep venous thrombosis was 1.72. Among patients aged 18-39 years, the relative risk of deep venous thrombosis was 6.81. From 1991-2005, after venous ultrasound was generally available, the relative risk of deep venous thrombosis (all ages) was 1.77.

Conclusion

The nephrotic syndrome is a risk factor for venous thromboembolism. This is strikingly apparent in young adults. Renal vein thrombosis was uncommon. Therefore, pulmonary embolism, if it occurs, is likely to be due to deep venous thrombosis and not renal vein thrombosis.     

Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia

The optimal management of hematologic malignancy‐associated venous thromboembolism (VTE) in patients with moderate‐to‐severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty‐seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000–45,000/µL) versus 165,000/µL (50,000–429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1–35 days). Therapy during the period of significant thrombocytopenia included prophylactic‐dose low‐molecular‐weight heparin ( LMWH) (47%), therapeutic‐dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow‐up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21–1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05–1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic‐dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy‐associated VTE. Am. J. Hematol. 91:E468–E472, 2016. © 2016 Wiley Periodicals, Inc.     

Venous thromboembolism in patients with ischemic and hemorrhagic stroke

The rates of pulmonary embolism (PE), deep venous thrombosis (DVT), and their combination, venous thromboembolism (VTE), in hospitalized patients with stroke from 1979 to 2003 were determined from the National Hospital Discharge Survey. Of 14,109,000 patients hospitalized with ischemic stroke, PE occurred in 72,000 (0.51%), DVT in 104,000 (0.74%), and VTE in 165,000 (1.17%). Of 1,606,000 patients hospitalized with hemorrhagic stroke, rates were higher: PE occurred in 11,000 (0.68%), DVT in 22,000 (1.37%), and VTE in 31,000 (1.93%). The rates of VTE with ischemic stroke and with hemorrhagic stroke did not change over the 25-year period of observation.     

精神药物在老年病人中的应用

随着我国老年人口不断增加，老年人的精神卫生问题逐渐为公众所关注。但在患有精神障碍的老年人中，他们初次就诊所遇到的通常是基层内科医生，此外，在一些伴有躯体疾患(如：感染、慢性疾病、肿瘤等)的老人住院治疗过程中常会出现这样和那样精神障碍。因此，如何正确、合理地使用精神药物，对这部分老年病人的康复起着十分重要的作用。     

Insulin sensitivity, adjusted beta-cell function and adiponectinaemia among lean drug-naive schizophrenic patients treated with atypical antipsychotic drugs: a nine-month prospective study

Atypical antipsychotic drugs (AADs) induce weight gain and truncal adiposity, and even the metabolic syndrome (MetS), which may progress to IFG/IGT or DM. AAD effects in lean schizophrenic patients without MetS have not been documented, especially in terms of weight gain and changes in insulin sensitivity (S), beta-cell function (beta) and adiponectinaemia. We prospectively determined the effects of nine-month therapy with AADs on anthropometrics, metabolism and adiponectinaemia, including homoeostasis model assessment (HOMA) modelling of S, beta and betaxS (hyperbolic product, assessing individual beta adjusted for S). We analyzed 36 schizophrenic subjects (M/F: 24/12; Caucasian: n=23, North African: n=12, South Asian: n=1) aged 35+/- years (mean+/-one S.D.) free of MetS (NCEP-ATPIII), of whom 19 study completers were evaluated following AAD treatment. S, beta, betaxS and adiponectin were measured at zero, three and nine months. At nine months, BMI had risen from 22+/-2 to 25+/-2kg/m(2) (P<0.001) and waist circumference from 85+/-8 to 91+/-11cm (P<0.001), while adiponectin decreased from 10.4+/-5.1 to 7.4+/-3.8mug/mL (P<0.001). Blood pressure and lipids were unaffected. S decreased from 138+/-49 to 110+/-58% (P=0.006) and beta increased from 83+/-24 to 100+/-40% (P=0.034). As a result, betaxS decreased from 106+/-19 to 91+/-27% (P=0.015). Fasting glycaemia rose from 89+/-5 to 96+/-9mg/dL (P=0.007). On study completion, 21% had IFG. Long-term use of AADs in lean, drug-naive, schizophrenics initially free of MetS induced weight gain and truncal fat accumulation associated with decreases in adiponectin and hyperbolic product, explaining the increased fasting glycaemia and impaired fasting glucose seen in predisposed individuals.     

Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia

Thromboembolic phenomena have been described in patients with thalassaemia intermedia and major, although there are relatively few epidemiological data on the overall frequency of these complications. To obtain more insight into the risk and mechanism of venous thromboembolism in thalassaemia, the aims of this study were: (i) to establish retrospectively the prevalence of thromboembolic events in a large group of adults with thalassaemia intermedia and major during a follow up period of 10 years; (ii) to measure in subgroups of these patients sensitive markers of activation of coagulation and fibrinolysis enzymes; and (iii) to look for possible procoagulant mechanisms. A high prevalence of thromboembolic events was found, particularly in splenectomized patients with thalassaemia intermedia (29%). These patients had high plasma levels of markers of coagulation and fibrinolysis activation. Furthermore, thalassaemic red cells and erythroid precursors from splenectomized patients with thalassaemia intermedia had an enhanced capacity to generate thrombin. To evaluate the role of splenectomy per se on procoagulant activity, we evaluated the capacity to form thrombin in healthy individuals who had been splenectomized for trauma. They produced the same amount of thrombin as non-splenectomized controls. In conclusion, the results of this study show the existence of a hypercoagulable state in splenectomized patients with thalassaemia intermedia and that their red and erythroid cells are capable of acting as activated platelets in thrombin generation.     

Venous and arterial thromboembolism in patients with inflammatory bowel diseases

The risk of thromboembolism (TE) is increased in patients with inflammatory bowel disease (IBD), mainly due to an increased risk of venous TE (VTE). The risk of arterial TE (ATE) is less pronounced, but an increased risk of cardiovascular diseases needs to be addressed in IBD patients. IBD predisposes to arterial and venous thrombosis through similar prothrombotic mechanisms, including triggering activation of coagulation, in part mediated by impairment of the intestinal barrier and released bacterial components. VTE in IBD has clinical specificities, i.e., an earlier first episode in life, high rates during both active and remission stages, higher recurrence rates, and poor prognosis. The increased likelihood of VTE in IBD patients may be related to surgery, the use of medications such as corticosteroids or tofacitinib, whereas infliximab is antithrombotic. Long-term complications of VTE can include post-thrombotic syndrome and high recurrence rate during post-hospital discharge. A global clot lysis assay may be useful in identifying patients with IBD who are at risk for TE. Many VTEs occur in IBD outpatients; therefore, outpatient prophylaxis in high-risk patients is recommended. It is crucial to continue focusing on prevention and adequate treatment of VTE in patients with IBD.     

Venous thromboembolism in intensive care patients

Venous thromboembolism frequently complicates the management of patients with severe medical and surgical illnesses. Because the diagnosis of VTE is especially challenging in critically ill patients, the focus of intensivists should be on characterization of risk factors and the appropriate choice of VTE prophylaxis. LDUH or LMHW is the preferred choice for VTE prophylaxis in ICU patients. Mechanical methods of prophylaxis should be reserved for patients with a high risk for bleeding. The effectiveness of mechanical methods and of combined strategies of prevention and the clinically important outcomes of therapy need to be explored further in critically ill patients. Few diagnostic strategies have been assessed in ICU patients with suspected PE. Ventilation-perfusion lung scans remain a pivotal diagnostic test but retain the same limitations in critically ill patients as seen in other patient populations. Newer noninvasive techniques, such as spiral CT associated with imaging of the extremities, are gaining more wide-spread use, but, thus far, pulmonary angiography remains the most reliable technique to confirm or exclude PE in patients with respiratory failure. A consensus must be reached regarding the most appropriate combination of tests for adequate and cost-effective diagnosis of VTE. Further investigation of diagnostic strategies that include adequate consideration of clinical diagnosis using standardized models and noninvasive imaging are warranted.     

Venous thromboembolism in COPD hospitalized patients

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for venous thromboembolism (VTE). We analyzed a large Spanish database to determine the incidence of VTE in these patients during hospitalization. A retrospective chart review of cohort of consecutive patients admitted with COPD as the primary reason for discharge in Spain between January 1st 2006 and December 31st 2007 was performed. For each patient, demographic data, risk factors for VTE and the diagnosis of VTE during hospitalization was recorded. We analyzed the clinical data of 313,233 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, in 2006 and 2007. We identify 3,562 new diagnosed VTE events among 270,840 COPD patients hospitalized more than two days (incidence 1.32%). Hospitalized-acquired VTE risk factors were male gender (odds ratio [OR] 1.77; CI95% 1.66–1.90), neoplasic disease (OR 2.93 CI95% 2.69–3.16, systemic arterial disease (OR 1.17 CI95% 1.10–1.36), decubitus ulcer (OR 1.19 CI95% 1.01–1.43), diabetes (OR 0.74 IC95% 0.69–0.81), and atrial fibrillation (OR 0.79 CI95% 0.72–0.87). VTE appears as a major threat to patients admitted for acute exacerbation of COPD, and pharmacologic prophylaxis should be considered in all high risk situations.     

Venous thromboembolism prophylaxis in medical patients

PURPOSE OF REVIEW: Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, represents a significant source of morbidity and mortality in the United States and worldwide. Most acutely ill medical patients are at risk for venous thromboembolism, and prophylaxis is recommended. However, acutely ill medical patients are heterogeneous, and the degrees of risk, the length of prophylaxis, as well as the most safe and efficacious strategies to prevent venous thromboembolism in specific medical patients continue to evolve. RECENT FINDINGS: Most medically ill patients in the hospital do not receive any form of venous thromboembolism prophylaxis despite evidence that their venous thromboembolism risk is similar to surgical patients. Low-molecular weight heparins demonstrate at least equal efficacy and improved safety over standard unfractionated heparin for the prevention of venous thromboembolism in medical patients. Patients with renal impairment, obesity, or those who are critically ill are special populations for prophylaxis that require individual approaches. Many patients recently discharged from the hospital remain at high risk for thrombosis. SUMMARY: All hospitalized patients should be assessed for venous thromboembolism risk. Most acutely ill medical patients will be in the high- to very high-risk category for thrombosis. Patients who have an estimated thrombosis risk greater than bleeding risk should receive pharmacologic prophylaxis. Low-molecular weight heparin is the preferred drug-based approach over standard unfractionated heparin for the prevention of venous thromboembolism in the acutely ill medical patient. Patients with higher risks for bleeding than thrombosis should receive mechanical methods of prophylaxis. Patients who have not returned to baseline health should be considered for extended venous thromboembolism prophylaxis out of the hospital.     

Diabetes mellitus and other metabolic disturbances induced by atypical antipsychotic agents

Atypical antipsychotic agents offer significant advantages over older conventional antipsychotic agents. The reduction in antipsychotic drug-associated extrapyramidal symptoms and the potential reduced risk for tardive dyskinesia, compared to conventional drugs, are major advances in the treatment of psychotic patients. However, recent reports of hyperglycemia, new-onset diabetes mellitus, diabetic ketoacidosis, weight gain, and lipid abnormalities associated with atypical antipsychotic agents have emerged. A review of the recent literature and an approach to the evaluation of risk factors to aide in the safe use of atypical antipsychotic agents is presented.