Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian,nationwide, population-based study

Background

Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients.

Methods

The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap?≥?60 days) during the first year of therapy.

Results

Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and ‘other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and ‘other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation.

Conclusion

ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.     

Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh

Global emergence and dissemination of carbapenemases are clinically threatening, notably in countries with endemic bla_NDM. To analyze the extent of carbapenemases in Bangladesh, 71 isolates were collected from 7 different clinical sources: wound swab (n = 38), pus (n = 13), urine (n = 9), blood (n = 4), tracheal aspirate (n = 3), pleural fluid (n = 1) and vaginal swab (n = 3) from Dhaka Medical College Hospital, Bangladesh. Among the isolates, 25 were resistant to at least one of the three carbapenems (imipenem, meropenem and doripenem), including 15 being resistant to all. These resistant isolates were identified as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, P. hibiscicola, Proteus mirabilis, Providencia stuartii and Citrobacter sedlakii. Carbapenemase detection among these 25 isolates varied in individual phenotypic assays (83% in Modified Hodge Test, 50% in Combined Disk Test for Metallo-β-lactamase prediction) as compared with the genotypes observed (96% prevalence of various carbapenemases including bla_OXA-1,48, bla_NDM-1,5, bla_VIM-2,5). bla_OXA-48 was the most prevalent gene (84%) followed by bla_NDM (72%). Coexistence of multiple gene combination such as bla_NDM+bla_OXA-48+bla_OXA-1 was prevalent (48%). Harborage of bla_VIM-5 (n = 1) was characterized for the first time, while bla_NDM-5 (n = 5) was reported contemporarily with a recent study in Bangladesh. Presence of plasmids (64%) and integron class 1 (100%) signifies the transferable potential of resistant traits. The emergence of such new variants along with the presence of the mobile genetic elements demands strict surveillance and combating strategies.     

Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28 μM versus 32.8±3.01 μM, P<0.002; and 0.175±0.05 versus 1.05±0.23, P<0.005, respectively). The effect of rosiglitazone in rats fed the control diet was not prominent. On the other hand, administration of rosiglitazone to the rats on the 1% L-methionine diet significantly reduced the levels of serum tHcy (16.6±2.1 μM versus 32.8±3.01 μM, P<0.001); however, the tHcy levels remained significantly elevated compared with animals on the control diet (P<0.002). The group receiving the L-methionine diet plus rosiglitazone had an inhibition in the development of IH compared with those receiving the L-methionine diet alone (I/M of 0.278±0.041 versus 1.05±0.23, P<0.01). Moreover, the development of IH in the group receiving the L-methionine diet plus rosiglitazone treatment was not significantly different from that observed in the group on the control diet without rosiglitazone (0.278±0.041 versus 0.175±0.05, respectively). These findings may have important implications in deciphering the molecular mechanisms involved in the augmentation of IH in HHcy and modulation of this process by rosiglitazone.     

Recombinant factor VIIa enhances deposition of platelets with congenital or acquired alpha IIb beta 3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor-independent thrombin generation

A novel approach to treat bleeding episodes in patients with Glanzmann thrombasthenia (GT) and perhaps also in patients receiving alpha IIb beta 3 inhibitors is the administration of recombinant factor VIIa (rFVIIa). The mechanism of action of rFVIIa in these patients is, however, still unclear. We studied the effect of rFVIIa-mediated thrombin formation on adhesion of alpha IIb beta 3-deficient platelets under flow conditions. Adhesion of alpha IIb beta 3-deficient platelets to the extracellular matrix (ECM) of stimulated human umbilical vein endothelial cells or to collagen type III was studied using a model system with washed platelets and red cells. When alpha IIb beta 3-deficient platelets were perfused over the surface at arterial shear rate for 5 minutes, a low surface coverage was observed (GT platelets, mean +/- SEM, 37.5% +/- 5.0%; normal platelets preincubated with an RGD-containing peptide, 7.4% +/- 2.1%). When rFVIIa, together with factors X and II, was added to the perfusate, platelet deposition significantly increased (GT platelets, mean +/- SEM, 67.0% +/- 4.3%; normal platelets preincubated with an RGD-containing peptide, 48.2% +/- 2.9%). The same effect was observed when normal platelets were pretreated with the commercially available anti-alpha IIb beta 3 drugs abciximab, eptifibatide, or tirofiban. It was shown that tissue factor-independent thrombin generation (presumably induced by binding of rFVIIa to adhered platelets) was responsible for the increase in platelet deposition. In conclusion, defective adhesion of alpha IIb beta 3-deficient platelets to ECM can be restored by tissue factor-independent rFVIIa-mediated thrombin formation. The enhanced generation of platelet procoagulant surface facilitates fibrin formation, so that lack of platelet aggregate formation might be compensated for.     

Prevalence of diabetes and prediabetes and their risk factors among Bangladeshi adults: a nationwide survey

Objective

To estimate the prevalence of diabetes and prediabetes in Bangladesh using national survey data and to identify risk factors.

Methods

Sociodemographic and anthropometric data and data on blood pressure and blood glucose levels were obtained for 7541 adults aged 35 years or more from the biomarker sample of the 2011 Bangladesh Demographic and Health Survey (DHS), which was a nationally representative survey with a stratified, multistage, cluster sampling design. Risk factors for diabetes and prediabetes were identified using multilevel logistic regression models, with adjustment for clustering within households and communities.

Findings

The overall age-adjusted prevalence of diabetes and prediabetes was 9.7% and 22.4%, respectively. Among urban residents, the age-adjusted prevalence of diabetes was 15.2% compared with 8.3% among rural residents. In total, 56.0% of diabetics were not aware they had the condition and only 39.5% were receiving treatment regularly. The likelihood of diabetes in individuals aged 55 to 59 years was almost double that in those aged 35 to 39 years. Study participants from the richest households were more likely to have diabetes than those from the poorest. In addition, the likelihood of diabetes was also significantly associated with educational level, body weight and the presence of hypertension. The prevalence of diabetes varied significantly with region of residence.

Conclusion

Almost one in ten adults in Bangladesh was found to have diabetes, which has recently become a major public health issue. Urgent action is needed to counter the rise in diabetes through better detection, awareness, prevention and treatment.     

Ameliorative effect of vitamin C on the haematological changes induced by exposure of chlorpyriphos and lead acetate in Wistar rats

The present study was designed to evaluate the effects of chlorpyriphos, lead acetate and vitamin C alone and in combinations, on various haematological parameters in Wistar rats. Rats of 150–200 g body weight were divided into eight groups of six animals each and were subjected to various daily oral treatment regimes for 98 days. Group C served as control receiving only corn oil, group CP received chlorpyriphos at 5.5 mg/kg in corn oil and group L received lead acetate at100?ppm in water, whereas animals in group CP + L received a combination of chlorpyriphos at 5.5 mg/kg in corn oil and lead acetate at 100 ppm in water. Group VC received vitamin C at 100 mg/kg in water; group CP + VC received a combination of chlorpyriphos at 5.5 mg/kg and vitamin C at 100 mg/kg; group L + VC received lead acetate at 100 ppm in water and vitamin C at 100 mg/kg and group CP + L + VC received chlorpyriphos at 5.5 mg/kg, lead acetate at 100 ppm in water and vitamin C at 100 mg/kg. Blood samples were collected on days 0, 30, 60 and 98 post exposure and analysed for packed cell volume (PCV), total erythrocyte count (TEC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total leucocyte count (TLC) and differential leucocyte count. A significant decrease in TEC, PCV and Hb and a significant increase in ESR values were observed. However, lead acetate caused an increase in TLC while chlorpyriphos resulted in a decrease in TLC. Both of these toxicants potentiated toxicity of each other. The study demonstrated that treatment of chlorpyriphos- and lead-treated rats with vitamin C significantly altered some of the important haematological parameters revealing the protective effect of this vitamin against haematological alterations induced by chlorpyriphos and lead.     

Poncet’s disease (reactive arthritis associated with tuberculosis): retrospective case series and review of literature

The primary objective of this study is to describe the demographics and clinical characteristics of patients with Poncet’s disease (PD) in the Makkah region in Saudi Arabia, where tuberculosis is on the rise. The secondary objective is conducting a PD systematic literature review to compare our findings. We studied seven patients who presented with arthritis within the first 3?years from diagnosis of active tuberculosis in two centers in the Makkah region: King Faisal Specialist Hospital and King Fahad Hospital in Jeddah from January 2005 to December 2011. We conducted a literature review on PD in multiple biomedical/pharmaceutical databases up to December 2011. We detected a new pattern of reactive arthritis associated with tuberculosis (TB). We identified this as PD or tuberculous rheumatism, which is a sterile reactive arthritis that can emerge during any stage of acute TB infection. Seven cases of Poncet’s disease were identified in our study. The most common presentation was extrapulmonary with involvement of multiple sites. Six out of seven patients developed arthritis after initiation of anti-TB drugs; one patient developed polyarthritis after completion of anti-TB medication. Asymmetrical polyarthritis was the most common presentation and the resolution of the arthritis was with symptomatic treatment and continuation of anti-TB drugs except in one case. PD may manifest in a variable pattern during the course of active tuberculous infection. Physicians should be aware of this rare complication associated with a common disease to prevent delay in diagnosis and initiation of appropriate treatment.     

Effect of combined oral contraceptives on bone mineral density in pre and postmenopausal women

A retrospective urban-based cross-sectional study was done in the department of Pharmacology in collaboration with the department of Obs and Gynae of BSSMU, Dhaka, to define any relation between the OCP and BMD in pre and postmenopausal women. A total of 100 closely matched healthy women were selected non-randomly. The age range was 35-55 years. Among them 50 were controls or nonuser and 50 were case or users of OCP. They were further subdivided into pre and postmenopausal groups. Bone density of the 100 women was measured in distal radius and ulna by single photon Absorptiometry Bone Densitometer DTX-100. Statistically significant higher bone mineral density (BMD) was found in oral combined OCP users than non-users, both in pre and postmenopausal women. It can be concluded from this study that the most important non-contraceptive benefit of OCP may be positive effects on bone mass and thus reduced risk of postmenopausal osteoporosis and osteroporotic fracture.     

A comparative study of body iron status and lipid profile in acute myocardial infarction patients

This study was carried out to evaluate the relationship between body iron status and lipid profile in hospital admitted clinically diagnosed AMI patients considering the concept that there is a potential association between body iron status and coronary heart disease (CHD). Total 80 subjects were selected, of which 40 were healthy adults and 40 were AMI patients. Fasting blood samples were collected from healthy adults. Blood samples of AMI patients were collected within 24 hours of the attack of myocardial infarction. Body iron status was measured in term of 3 variables serum total iron concentration, TIBC and transferrin saturation. Lipid profile variables measure were total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. No correlation was found between serum iron and the variables of lipid profile. TIBC was found to maintain negative correlation with total cholesterol, triglyceride and LDL-cholesterol but positive correlation with HDL-cholesterol. Transferrin saturation was found to maintain strongly positive correlation with total cholesterol, triglyceride and LDL-cholesterol but strongly negative correlation with HDL-cholesterol. This correlation of TIBC and transferrin saturation with lipid profile supports the hypothesis that there is a potential association between body iron status and coronary heart disease.     

Insight into illness and attitudes toward medications among inpatients with schizophrenia

This study assessed symptoms, severity of illness functional level, insight into illness, and attitudes toward medication in a sample of psychiatric patients who were newly admitted to a state hospital. The patients were evaluated before and after treatment with atypical, conventional, or mixed (atypical plus conventional) antipsychotic medication regimens with the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression, the Global Assessment of Functioning, the Scale to Assess Unawareness of Mental Disorder, and the Drug Attitude Inventory. Overall, the patients showed significant improvement in symptoms, severity of illness, functional level, and insight into their illness during the course of hospitalization. Their attitudes toward medications changed minimally during treatment. Only the patients who were treated with conventional antipsychotics showed significant improvement in their attitudes toward medication. However, the change was not large enough to differentiate the conventional antipsychotic treatment group from the other treatment groups.