Episodes Of Use Research Articles

Concomitant use of statins and macrolide antibiotics and risk of serious renal events: A nationwide cohort study

BackgroundConcomitant use of statins metabolized by the cytochrome P450 isoenzyme 3A4 (CYP3A4) and CYP3A4-inhibiting macrolide antibiotics may confer an increased risk of renal failure. We investigated the risk of serious renal events associated with concomitant use of such statins and such macrolides. MethodsIn a nationwide register-based cohort study (Denmark, 1999–2017), we identified 906,423 new users (40–79 years old), of CYP3A4-metabolized statins. In propensity score-matched analyses, we compared the risk of serious renal events during episodes of concomitant use of statins and CYP3A4-inhibiting macrolides (n = 71,521) with episodes of use of statins alone (n = 285,488) and, as the primary analysis, with episodes of concomitant use of statins and an active comparator (penicillin V, n = 139,446). Using proportional hazards regression, we estimated hazard ratios (HRs) for serious renal events within 30 days of start of follow-up. ResultsWe observed 25 serious renal events during concomitant use of statins and macrolides (incidence rate [IR], 4.9 per 1000 person-years). Compared with use of statins alone (50 events; IR, 2.3), concomitant use of statins and macrolides was associated with a significantly increased risk of serious renal events (HR 2.16, 95% confidence interval [CI] 1.33, 3.49). Compared with concomitant use of statins and penicillin V (52 events; IR, 5.3), however, we observed no increased risk (HR 0.93, 95% CI 0.58, 1.49). ConclusionsIn this nationwide cohort study concomitant use of statins and macrolides was not associated with a significantly increased risk of serious renal events.

Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis.

Case reports and pharmacokinetic studies have suggested that concomitant use of low-dose methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low-dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis. The study was conducted as a register-based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n=21536) and control episodes of use of methotrexate alone (n=21725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional-hazards regression, with adjustment using inverse-probability-of-treatment weighting based on propensity scores. During follow-up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person-years) and 129 during control episodes (11.0 per 1000 person-years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07-1.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia. Concomitant use of low-dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low-dose methotrexate and NSAID are coprescribed.

Use of Proton Pump Inhibitors and the Risk of Acute Kidney Injury Among Patients with Rheumatoid Arthritis: Cohort Study.

Recent observational studies have indicated that use of proton pump inhibitors may be associated with adverse renal outcomes. The objective of this study was to investigate whether the use of proton pump inhibitors increases the risk of acute kidney injury among patients with rheumatoid arthritis. We conducted the study as a historical prospective cohort study, including patients with rheumatoid arthritis, 30-84years of age, during 2004-2015. Among these, we identified and matched episodes of use and non-use of proton pump inhibitors (control episodes) 1:4 on the propensity score, including 24,579 episodes of use of proton pump inhibitors and 98,230 control episodes. The primary outcome was a first diagnosis of acute kidney injury and the secondary outcome was any serious renal event (acute kidney injury or chronic kidney disease). The primary time point for analysis was 120 days after study entry. The incidence rate of acute kidney injury was 2.2 per 1000 person-years during episodes of use of proton pump inhibitors and 0.9 during control episodes. Use of proton pump inhibitors was associated with a significantly increased risk of acute kidney injury (hazard ratio 2.30, 95% confidence interval 1.26-4.20). The absolute risk difference was 40 (95% confidence interval 8-99) events of acute kidney injury per 100,000 episodes of use of proton pump inhibitors. Use of proton pump inhibitors was also associated with a significantly increased risk of the secondary outcome of any serious renal event (hazard ratio 2.61, 95% confidence interval 1.80-3.80). This cohort study among patients with rheumatoid arthritis found a significantly increased risk of acute kidney injury associated with the use of proton pump inhibitors. These findings may help inform clinical decision making when considering the risks and benefits of proton pump inhibitor treatment in rheumatoid arthritis.

Patterns of use of long-acting bronchodilators in patients with COPD: A nationwide follow-up study of new users in New Zealand.

While several studies have found that prescribing practices do not conform to chronic obstructive pulmonary disease (COPD) treatment guidelines, none have examined longitudinal patterns of use of long-acting beta2 -agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy across an entire country. We undertook a nationwide follow-up study to describe treatment patterns in new users of long-acting bronchodilators. National health and pharmaceutical dispensing data were used to identify patients aged ≥45 years who initiated LABA and/or LAMA therapy for COPD between 1 February 2006 and 31 December 2013. Dispensings of LABAs, LAMAs and inhaled corticosteroids (ICSs) were aggregated into episodes of use of therapeutic regimens. Kaplan-Meier curves, sunburst plots and sequence index plots were generated to summarize, respectively, the duration of the first regimen, the sequences in which unique regimens were used and the patterns of use and non-use during follow-up. The study cohort included 83 435 patients with 290 400 person-years of follow-up. The most commonly initiated regimen was a LABA with an ICS. ICS use was inconsistent with international guidelines: over- and under-treatment occurred in patients with infrequent and frequent exacerbations, respectively, and ICS monotherapy was common. The median duration of the first regimen was 46 days. Many patients used multiple regimens over time and periods of non-use were common. In this nationwide study, patterns of use of LABAs, LAMAs and ICSs were complex and often did not comply with treatment guidelines. Further work is required to address the discrepancy between guidelines and prescribing practices.

Amphetamine-Induced Delusional Infestation

Amphetamine-Induced Delusional Infestation

Type 2 Diabetes Mellitus Treatment Patterns Across Europe: A Population-based Multi-database Study

PurposeThe aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. MethodsPrescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns. FindingsA total of 253,530 patients initiating T2DM treatment during the study period were included; 52% to 55% were male, and the mean age ranged from 62 to 67 years. Metformin was the most common initial treatment in all countries. After initial therapy, most patients in the Netherlands, Spain, and the United Kingdom switched to a combination of metformin + a sulfonylurea derivative (SU). In Italy, metformin in combination with an SU was outnumbered by “other treatment,” mainly because of repaglinide use. In France, treatments including dipeptidyl peptidase-4 inhibitors were most frequent as second- and fourth-line treatment. Metformin monotherapy was again most commonly observed as the third line of treatment in all countries. Fourth treatment was a combination of metformin + an SU in the Netherlands and Spain; in the United Kingdom and France, dipeptidyl peptidase-4 inhibitors were the most frequently used fourth line of treatment. ImplicationsThis study provides a comprehensive overview of T2DM treatment patterns among patients initiating T2DM treatment in 5 European countries. There were differences, especially regarding the uptake of newer incretin-based treatments, which are usually prescribed as a second and/or third treatment in agreement with local guidelines. These variations reflect the differences between the national guidelines of these countries.

Architecture of relict charcoal hearths in northwestern Connecticut, USA

AbstractRelict charcoal hearths are round or elliptical earthen platforms up to 11 m in diameter and a widespread feature of historical industry that supplied charcoal used in the production of iron in furnaces or smelters. The iron industry dominated Litchfield County, Connecticut, and surrounding areas in the northeast United States throughout the 19th century, peaking in ∼1850. The large number of charcoal hearths in this region is a relic of >150 years of widespread iron production. In this study, we describe the architecture and soil stratigraphy of 26 charcoal hearths in Litchfield County. This contribution aims to (1) compare soils that comprise the charcoal hearths with “natural” adjacent soils, (2) measure the thickness of topsoil developed upon the hearths, and (3) characterize the stratigraphy associated with these features. Results indicate that the black topsoils overlying the charcoal hearths contain residual charcoal and are on average 2.6 times thicker than adjacent Cambisols. Charcoal hearths display two or more black, charcoal‐rich strata separated by layers of reddish‐brown soil low in charcoal content indicating multiple episodes of use. We also find that many charcoal hearths have been stabilized with boulders on the downslope side during construction and repeated use. Overall, the results presented here provide significant information regarding the construction, use, and associated impacts of earthen platforms for charcoal production in the northeast United States, with further relevance to other areas where historical charcoal production occurred.

Cesspits and the P-P-P-P-problem: The pitfall of the Pompeii premise and the palimpsest

Given their high yield of artefacts and ecofacts, cesspits are afforded much time and effort in urban archaeology. While historical sources reveal that cesspits were emptied at regular intervals every few years, archaeologists still treat cesspits as closed contexts where artefacts lie fossilized and undisturbed by subsequent cultural or natural processes. This ‘archaeological blind spot’ results from the application of traditional archaeological methods without sufficient attention being paid to cesspit cleaning activities.This article calls for a re-evaluation of the formation processes associated with archaeological examples of cesspits and for an integrated analysis of the different materials—ceramics, organics, etc.—that are present. These may have entered the cesspit at different times as a result of successive episodes of use and cleaning, resulting in different dates for the cesspit, all of which may be valid in defining its history. If artefacts and ecofacts are studied in isolation from the other materials in the cesspit without a full understanding of its formation and stratigraphy, the result may be quite misleading.

Patterns and trends in long-term opioid use for non-cancer pain in British Columbia, 2005-2012.

We aimed to calculate trends in incidence and prevalence rates of long-term opioid use for non-cancer pain, as well as to describe the characteristics of long-term opioid users and their patterns of opioid use. We used population-based linked health care and socio-demographic administrative data for British Columbia (BC) between 2005 and 2012. We included individuals who had at least one episode of long-term opioid use during the study period and who were not cancer or palliative care patients. Long-term users comprised only 10% of all individuals prescribed opioids for non-cancer pain, but accounted for 64% of all opioid prescriptions and 87% of all morphine equivalents dispensed in BC during this period. While the incidence rate did not significantly change, the prevalence rate increased by 27% for men and 22% for women. In 2012, there were 3.80 (3.72-3.88) new long-term opioid users per 1,000 men and 4.42 (4.34-4.51) new users per 1,000 women. At the same time, there were 18.3 (95% CI 18.1-18.5) existing long-term users per 1,000 men and 21.7 users (95% CI 21.5-21.9) per 1,000 women. Overall, 2.4% of BC residents were long-term users of prescription opioids in 2012. Most long-term users had one continuous episode of use spanning multiple years. Almost two thirds took opioids every other day or more frequently. There is a growing population of long-term opioid users for non-cancer pain in BC, with higher incidence and prevalence rates observed among women than among men.

Typical-use contraceptive failure rates in 43 countries with Demographic and Health Survey data: summary of a detailed report

BackgroundWhile most unintended pregnancies occur because couples do not use contraception, contraceptive failure is also an important underlying cause. However, few recent studies outside of the United States have estimated contraceptive failure rates, and most such studies have been restricted to married women, to a limited number of countries and to 12-month failure rate estimates. MethodsUsing self-reported data from 43 countries with Demographic and Health Survey data, we estimated typical-use contraceptive failure rates for seven contraceptive methods at 12, 24 and 36months of use. We provide a median estimate for each method across 43 countries overall, in seven subregions and in individual countries. We assess differences by various demographic and socioeconomic characteristics. Estimates are not corrected for potential errors in retrospective reporting contraceptive use or potential underreporting of abortion, which may vary by country and subgroups within countries. ResultsAcross all included countries, reported 12-month typical-use failure rates were lowest for users of longer-acting methods such as implants (0.6 failures per 100 episodes of use), intrauterine devices (1.4) and injectables (1.7); intermediate for users of short-term resupply methods such as oral contraceptive pills (5.5) and male condoms (5.4); and highest for users of traditional methods such as withdrawal (13.4) or periodic abstinence (13.9), a group largely using calendar rhythm. ConclusionsOur findings help us to highlight those methods, subregions and population groups that may be in need of particular attention for improvements in policies and programs to address higher contraceptive failure rates.

G288 A regional review of humidified high flow nasal cannula oxygen use in children

The aims of this review were four fold To document the non-intensive care paediatric experience at a regional level of oxygen delivered via high flow humidified nasal cannulae (HHFNC). To understand patient outcomes and safety data with respect to HHFNC oxygen. To determine whether clinical data might help identify those children most likely to deteriorate on HHFNC oxygen. To create a region wide guideline based on the findings. Data was collected between October 2013 and April 2014. A pro forma was completed by local paediatric teams at all 10 hospitals within the regional critical care network on all episodes of the use of HHFNC oxygen. To inform guideline needs of the region, questionnaires about the use of HHFNC oxygen were completed by nursing and medical staff. 210 episodes of HHFNC oxygen use were captured. Experience with HHFNC oxygen varied widely within the region. It was used most frequently in children under a year of age diagnosed with bronchiolitis. Children with bronchiolitis who deteriorated whilst receiving HHFNC oxygen had a lower pH and higher work of breathing score two hours after commencing this form of respiratory support (Table 1). The proportion of infants with bronchiolitis receiving HHFNC oxygen who required intubation and ventilation was lower than found in a previous regional review in 2008 when continuous positive airways pressure (CPAP) was the standard means of providing respiratory support. Bronchiolitic infants receiving HHFNC oxygen remained less likely to require intubation, even when adjusted for initial pH The use of HHFNC oxygen has become widespread in our general paediatric population. Our review demonstrates that HHFNC oxygen is safe in children for a variety of conditions, ages and weights. The use of blood gases and assessment of work of breathing pre and two hours after starting HHFNC oxygen could help identify those at risk of deteriorating. There is a suggestion that HHFNC oxygen may reduce the intubation and ventilation rate of children with bronchiolitis. A regional guideline has been designed based on these findings.

Switch patterns of osteoporosis medication and its impact on persistence among postmenopausal women in the UK General Practice Research Database

This study aims to describe the switch patterns of osteoporosis medication in postmenopausal women and to explore the impact of switching on persistence. This study used a cohort of postmenopausal women who initiated the first treatment with osteoporosis medication between 1995 and 2008. Selected women had switched at least once to a different frequency or type of osteoporosis medication during follow-up. For each study woman, we identified the first therapy (initial osteoporosis medication), second therapy (medication received at first switch), and, where available, third therapy (medication received at second switch), regardless of how many times she switched during follow-up. Persistence was defined as the number of days from the index date to the end of the last prescription within each episode of use. The Kaplan-Meier method was used to calculate persistence rates at 6 months, 1 year, 3 years, and 5 years. Of 20,638 women who switched osteoporosis treatment at least once in the study period, approximately 67% switched once, 21% switched twice, and 12% switched three times or more. Persistence rates for the second therapy were highest (% [95% CI], 46.6 [46.1-47.1], 35.0 [34.5-35.5], 18.8 [18.3-19.3], and 11.4 [10.9-11.7] at 6 mo, 1 y, 3 y, and 5 y, respectively), whereas persistence rates for the first therapy were lowest (% [95% CI], 34.3 [33.9-34.8], 21.6 [21.2-21.9], 5.90 [5.68-6.13], and 1.57 [1.45-1.69], respectively). Among women who switch their initial medication, even though switching to the second medication improves persistence during the initial therapy, persistence on the second and subsequent therapies remains suboptimal.

It depends on when you ask: Motives for using marijuana assessed before versus after a marijuana use event

BackgroundMarijuana use motives are typically evaluated retrospectively using measures that summarize or generalize across episodes of use, which may compromise validity. Using Ecological Momentary Assessment data, we examined the main reason for a specific marijuana use event measured both prospectively and retrospectively. We then determined reason types, event characteristics, and user characteristics that predicted change in reason. MethodsThirty-six medical outpatients age 15 to 24 years who used marijuana two times a week or more used a handheld computer to select their main reason for use from the five categories of the Marijuana Motives Measure (Simons, Correia, & Carey, 1998) just before and after each time they used marijuana over two weeks (n=263 events with before/after reason). The reasons were examined individually and according to dimensions identified in motivational models of substance use (positive/negative, internal/external). ResultsThe reason assessed before use changed to a different reason after use for 20% of events: 10% of events for pleasure; 21%, to cope; 35%, to be more social; 55%, to expand my mind; and 100%, to conform. In the multivariable model, external and expansion reasons each predicted change in reason for use (p<0.0001 and p=0.001, respectively). Youth were also more likely to change their reason if older (p=0.04), if male (p=0.02), and with weekend use (p=0.002). ConclusionRetrospective assessments of event-specific motives for marijuana use may be unreliable and therefore invalid for a substantial minority of events, particularly if use is for external or expansion reasons.

ABSTRACT 101

Background and aims: When tertiary care for infants and children with impending respiratory failure (IRF) is 2500 km distant, local management has the potential to save costs of air-transport and family dislocation. Aims: To assess feasibility of minimally-invasive respiratory support (MIRS): humidified hi-flow oxygen and bubble-CPAP in IRF in conditions of known severity and estimate benefit from financial and social savings. Methods: Hi-Flow oxygen (max 2L/kg/min) escalating to bubble-CPAP (5-8cmH2O) on clinical and biochemical evidence of IRF was implemented in 29 neonates and 32 babies (average age 5.6, range 0 to 30 months) over a 24 month period. The modalities were introduced after staff training and approval by the regional Health Ethics Committee. Results: All 61 cases were successfully treated, with none requiring unanticipated evacuation. Episodes of use (mean duration hours): Hi-flow 35 (51); CPAP 31 (19 but most <8). 21 neonatal (72%) and 22 (68%) baby transfers were averted at an estimated $A1.4million saving in aero-medical. Savings from family dislocation to distant city: incalculable. Intubation rates decreased from 4.6 to 3.1 per 1000 separations following implementation of the program. Conclusions: MIRS for infants and children can be safely implemented in a remote centre to reduce aero-medical transfer with huge savings in financial cost and heartache to parents.

Use of Prescription Antiobesity Drugs in the United States

To examine national trends in prescription antiobesity drug use in the United States. Data analysis. The IMS Health Vector One National and Total Patient Tracker and Encuity Research Treatment Answers databases, the Source Healthcare Analytics Source Lx database, and IMS LifeLink database. National drug use estimates from 1991-2011 were extracted from the IMS Health Vector One National database, and patient characteristics from 2008-2011 were extracted from the Vector One Total Patient Tracker and Encuity Research Treatment Answers databases. The Source Healthcare Analytics Source Lx database was used to examine duration of antiobesity drug use from 2002-2011, with a sensitivity analysis performed using the IMS LifeLink database. In 2011, approximately 2.74 million patients used antiobesity drugs, predominantly phentermine (2.43 million patients). The use of prescription orlistat and sibutramine was relatively uncommon. Eighty-five percent of antiobesity drug users were female, 62% were aged 17-44years, and 4.5% had a body mass index of ≤24.9kg/m(2) . Duration of use was generally short and most patients only had one episode of antiobesity drug use during the observation period. The longest episode of use was30days or less in 47-58% of patients. Approximately one quarter of the patients used antiobesity drugs for longer than 90days, including phentermine and other amphetamine congeners whose labels recommend short-term use, not exceeding "a few weeks." Only 1.3-4.2% of antiobesity drug users used them for longer than1year. Concomitant use of two or more prescription weight-loss drugs was generally uncommon, although phentermine was dispensed during 13-16% of benzphetamine, diethylpropion, or phendimetrazine episodes of use. Phentermine dominated the prescription weight-loss market. Despite the indication of short-term use for amphetamine congeners, duration of use was similar to other antiobesity drugs. Nevertheless, the reasons for and implications of the limited duration of use observed with all prescription antiobesity drugs deserve further investigation.

Early discontinuation of treatment in patients with orthostatic hypotension

Midodrine and fludrocortisone are considered the first-line pharmacologic treatments for orthostatic hypotension (OH). Although OH is thought to require long-term therapy, it is unknown how long patients remain on treatment ("persistence"). We assembled a retrospective cohort of patients with OH aged ≥ 50 years enrolled in Tennessee Medicaid (1996-2008), and identified new episodes of midodrine and fludrocortisone use. Follow-up continued from the first medication fill through treatment discontinuation (90 days without medication), change in treatment, death, hospitalization, and loss of enrollment or study end. We compared persistence on treatment using Cox regression models and fludrocortisone as reference. Covariates included demographics, healthcare utilization measurements and co-morbidities. We identified 1704 OH patients, who initiated 1767 episodes of fludrocortisone (1103) or midodrine (664) use. The median age was 69 years, 53% were female and 80% were white. During 738 person years of follow-up, episodes of use ended because of treatment discontinuation in 467 (27% fludrocortisone, 25% midodrine); treatment change in 72 (3% fludrocortisone, 6% midodrine) and death in 53 (3% fludrocortisone, 2% midodrine). Overall median persistence on fludrocortisone and midodrine was 254 (IQR: 119-783) and 259 (IQR: 119-807) days, respectively. The adjusted hazard ratio (aHR) for overall non-persistence on midodrine compared to fludrocortisone was 1.07 (95% CI: 0.90-1.28). Overall duration of OH treatment with first-line medications was short, and similar for fludrocortisone and midodrine. Further research is warranted to determine the causes of this low persistence. (Words#234).

PS2-29: Comparison of Self-reported Oral Contraceptive Use and Automated Prescription Fills

Background/Aims Self-reported use of oral contraceptives (OCs) may be subject to recall bias. Previous reports comparing self-report OC use and computerized pharmacy data have focused on current use or longer-term use in younger women and have found (adjusted) kappa statistics of 79-85%. The objective of the current analysis was to evaluate the reliability of self-reported OC use obtained from a sample of peri- and early post-menopausal women. Methods Participants were 45-59 year-old women eligible for an ongoing population-based case-control study assessing the association between OC use and incident fractures around the menopausal transition. Cases were all women enrolled in Group Health with an ICD9 osteoporotic fracture code in 2008-2009; age-matched non-fracture controls were randomly selected. Eligible cases and controls (n=535) who reported at interview that they always/usually filled prescriptions at GH pharmacies and agreed to record review were included. Respondents who reported ever using OCs before the reference date (fracture date for cases; randomly assigned dates based on distribution of case dates for controls) were asked for each episode of use their age and length of use. A life events- calendar tool was available to interviewers. Computerized pharmacy information was obtained on OC fills back to 1977. OC use was based on GH pharmacy and First Data Bank OC class key ingredients [e.g. ethinyl estradiol levonorgestrel] and name. OC use was evaluated using >1 fill or >2 fills within a 1-year period. Ever use use since ages 35 38 and 40 and 5 years before reference date were examined. Women were required to be enrolled for the designated time period except for the ever-use category. We calculated kappa (K) the chance-corrected measure of agreement and the prevalence-adjusted bias-adjusted kappa (PABAK). Results The agreement between self-reported OC use and OC fills was highest for more recent use (PABAK=92% for OC use within 5 years of reference date and 55% for use at ages >38). Conclusion In women around the menopausal transition agreement between self-reported OC use and computerized OC prescription fills was moderate for use after age 38 and excellent for OC use within 5 years of the reference date.

O-58 - Suicide and suicide attempts during use of antidepressants: high risk at young age?

Introduction Since 2003, the Food and Drug Agency (FDA) issued a number of advisory warnings regarding the association between use of antidepressants (ADs) and suicidal behavior, especially among young people. These warnings have led to a more restrictive use of ADs, also among adults. Objectives We investigated the rates of (fatal) suicide attempts associated with different classes of ADs at different ages. Aims To contribute to finding a favorable balance between safety and the challenge to offer efficacious treatment. Methods By linking the Psychiatric Case Register Middle-Netherlands, which contains patients of psychiatric services in the Utrecht region, Agis Health Database, which contains registered insurance claims, and the death register of Statistics Netherlands, rates of (fatal) suicide attempts were estimated. Results For 7,725 patients with a depressive disorder (mean age 43.2 years) and with at least one AD delivery, 35,224 episodes of use, 23,840 episodes of no use, 32 suicide events, and 357 suicide attempts were established. No significant differences were found in suicide and suicide attempt rates between the different classes of ADs. Compared to episodes of no use, episodes of use of ADs were significantly associated with higher frequency of suicide attempts but suicide rates were similar. A trend towards an unfavorable effect of ADs on suicide risk at younger age was found (P = 0.0718). Conclusion Our results support the FDA advisories in which ADs are treated alike. Use of ADs is indicative of a high risk of suicide, which reiterates the need for close monitoring of patients, especially at young age.

Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel.Design Nested case-control...

Methamphetamine and lentivirus interactions: Reciprocal enhancement of central nervous system disease

Use of methamphetamine is increasingly a significant factor for the spread of human immunodeficiency virus type 1, for in certain populations, there is a convergence of methamphetamine abuse with human immunodeficiency virus type 1 infection. Methamphetamine and human immunodeficiency virus type 1 are both individually neuropathogenic, and the neuropathology caused by these two agents occurs in overlapping brain regions. However, the biological interaction of methamphetamine with lentiviruses remains unknown. Here, we investigate the effects of simultaneous exposure of these two agents on disease progression using the feline immunodeficiency virus model. The study models the bingeing methamphetamine user with sequential and repeated episodes of use, which were interrupted by periods of abstinence. Methamphetamine exposure significantly accelerated and enhanced the severity of the feline immunodeficiency virus model-induced central nervous system functional pathology, as measured in delays in brainstem auditory evoked potentials. Reciprocally, feline immunodeficiency virus enhanced the severity of the methamphetamine-induced effects on brain monoamine neurotransmitter and dopamine transporter levels. The results of this study indicate that a dual potentiation occurred. That is, methamphetamine enhanced feline immunodeficiency virus model-induced central nervous system disease and feline immunodeficiency virus model enhanced the toxic effects of methamphetamine, heralding a significant concern for those individuals that are exposed to both agents.