Diagnosis and treatment of adult attention-deficit/hyperactivity disorder at US ambulatory care visits from 1996 to 2003

OBJECTIVE: To determine national-estimates and characteristics of United States (US) ambulatory care visits made by adults, aged 18 years or older, with attention-deficit hyperactivity disorder (ADHD) diagnosis, treatment patterns, and significant factors associated with adult-ADHD treatment. METHODS: Retrospective analyses were conducted of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey over a combined 8-year period (1996-2003). Mental-health disorder (including ADHD) visits were identified using International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) diagnostic codes. Significant factors of adult-ADHD treatment were determined in multivariable logistic regression analyses. RESULTS: An estimated total 10.5 million ambulatory-ADHD visits accounted for 3.5% of 301 million adult mental-health disorder visits. The census-adjusted visit rate was 0.3-0.4%. Increasing in numbers from the year 2000, ADHD visits were most often to psychiatrists, by Caucasian men, aged 18 to 40 years. Significantly fewer ADHD visits without, versus with, psychiatric comorbidity (mainly depression) received various treatments-- behavioral (46% vs. 83%), antidepressant (18% vs. 66%), or combined behavioral and ADHD-specific (stimulant or atomoxetine) pharmacotherapy (36% vs. 57%) respectively. However, more ADHD visits without than with psychiatric comorbidity received ADHD-specific pharmacotherapy alone (76% vs. 68%) or no treatment (14% vs. 6.5%). At ADHD visits, adjusting for gender, age, and US census geographic-region, psychiatric comorbidity (odds ratio [OR], 6.5, 95% confidence interval [Cl], 3.5-12.4, p < 0.05) and self-pay reimbursement-source (OR, 2.7, 95% Cl, 1.3-5.7, p < 0.05) significantly increased the likelihood of behavioral treatment. Insurance reimbursement-sources other than private and self-pay significantly decreased the likelihood of an ADHD-specific pharmacotherapy (OR, 0.4, 95% Cl, 0.2-0.7, p < 0.05) or any ADHD-treatment (OR, 0.2, 95% Cl, 0.1-0.5, p < 0.05). CONCLUSIONS: Adult-ADHD visits have increased in recent years, with a census-adjusted visit rate of 0.3-0.4%. Psychiatric comorbidity and reimbursement-source were associated with ADHD-treatment. Limited treatment may be a significant problem in US-ambulatory care. It is important to continue validation studies, educate providers, examine the efficacy of multimodal-treatments, and study insurance-related barriers to adult ADHD-treatment.     

Current and emerging pharmacotherapy for the treatment of adult attention deficit hyperactivity disorder (ADHD)

ABSTRACT

Introduction: ADHD is characterized by a developmentally inappropriate level of inattentiveness, impulsivity and/or hyperactivity. In adults, the disorder is frequently accompanied by Emotional Dysregulation (ED), associated to a variety of related psychiatric comorbidities, complicating its recognition and treatment management.

Areas covered: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of pharmacotherapy in adults with ADHD and ED, other neurodevelopmental disorders, Bipolar Disorder (BD) and Anxiety Disorders (ADs). When controlled data are unavailable, the authors have included open-label and observational studies.

Expert opinion: ED in adult patients with ADHD is a very common and impairing problem that can be treated with stimulants or atomoxetine. ADHD studies in adults with other neurodevelopment disorders are scarce; stimulants seem to be the most effective and safe drugs in treating ADHD symptoms, without worsening the core features of other neurodevelopmental disorders. In patients with ADHD and comorbid BD, the treatment of BD alone may result in residual symptoms of ADHD. Patients should be treated hierarchically: BD should be treated first, while ADHD should be treated combining ADHD medications and mood stabilizers after mood stabilization. The available evidence for treating patients with ADHD and comorbid ADs in adults supports the idea of an anti-anxiety/ADHD-specific treatment association.     

Characteristics and patterns of healthcare utilization of patients with fibromyalgia in general practitioner settings in Germany

ABSTRACT

Objective: To examine characteristics and patterns of healthcare utilization of patients with fibromyalgia (FM) under the care of general practitioners (GPs) in Germany.

Research design and methods: Retrospective cohort study, using a large electronic database with information on GP encounters in Germany (IMS MediPlus). We identified all patients, aged ≥?18 years, with any encounters for FM (ICD-10 diagnosis code M79.7) between February 1, 2004 and January 31, 2007. We also constituted a comparison group consisting of randomly selected patients with one or more GP encounters – but none for FM – during this period, who we matched to FM patients based on age and sex. Characteristics and healthcare utilization of patients in the FM and comparison groups were then examined over the 1-year period, February 1, 2006–January 31, 2007.

Main outcome measures: Prevalence of co-morbidities; use of pain-related pharmacotherapy; number of GP office visits; number of specialist referrals; and number of sick notes (physician-excused absences from work).

Results: The study sample consisted of 4983 FM patients and an identical number in the comparison group. Mean age was 58 years; 87% were women. The prevalence of various co-morbidities was greater among FM patients, including painful neuropathies (33% vs. 18% for comparison group) and depression (20% vs. 5%) (both p?<?0.01); more FM patients also received pain-related pharmacotherapy (67% vs. 28%; p?<?0.01). Compared with patients in the comparison group, FM patients averaged approximately twice as many GP visits (11.4 [SD?=?10.1] vs. 5.8 [7.5]), referrals (4.5 [5.2] vs. 2.2 [3.6]), and sick notes (0.6 [1.8] vs. 0.3 [1.1]) (all p?<?0.01).

Limitations: Information in the study database is limited to GP encounters, and the sensitivity and specificity of our case-finding methods are unknown.

Conclusions: Patients with FM under the care of GPs in Germany have comparatively more co-morbidities and higher levels of healthcare utilization.     

Current status of cholesterol goal attainment after statin therapy among patients with hypercholesterolemia in Asian countries and region: the Return on Expenditure Achieved for Lipid Therapy in Asia (REALITY-Asia) study

ABSTRACT

Background: Data on achieving National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals in Asia are limited.

Objective: To examine treatment patterns, goal attainment, and factors influencing treatment among patients in 6 Asian countries who were taking statins.

Methods: A retrospective cohort study was conducted in China, Korea, Malaysia, Singapore, Taiwan, and Thailand, where 437 physicians (41% cardiologists) recruited adults with hypercholesterolemia newly initiated on statin monotherapy.

Results: Of 2622 patients meeting inclusion and exclusion criteria, approximately 66% had coronary heart disease (CHD)/diabetes mellitus, 24% had no CHD but ≥2 risk factors, and 10% had no CHD and <2 risk factors. Most patients (～90%) received statins at medium or lower equipotency doses. Across all cardiovascular risk categories, 48% of patients attained ATP III targets for low-density lipoprotein cholesterol (LDL-C), including 38% of those with CHD/diabetes (goal: <100 mg/dL), 62% of those without CHD but with ≥2 risk factors (goal: <130 mg/dL), and 81% of those without CHD and <2 risk factors (goal: <160 mg/dL). Most patients who achieved goals did so within the first 3 months. Increasing age (odds ratio (OR) = 1.015 per 1-year increment; 95% confidence interval (CI) = 1.005–1.206; p = 0.0038) and initial statin potency (OR = 2.253; 95% CI = 1.364–3.722; p = 0.0015) were directly associated with goal attainment, whereas increased cardiovascular risk (OR=0.085; 95% CI = 0.053–0.134; p < 0.0001 for CHD/diabetes mellitus at baseline compared with <2 risk factors,) and baseline LDL-C (OR = 0.990; 95% CI = 0.987–0.993); p < 0.0001 per 1-mg/dL increment) were inversely associated with LDL-C goal achievement. Limitations of this study include potential differences in treatment settings and cardiovascular risk factors between different countries and centers. In addition, the effects on cholesterol goal achievement of concomitant changes in lifestyle were not assessed.

Conclusion: LDL-C goal attainment is low in Asians, particularly those with CHD/diabetes. More effective patient monitoring, treatments, including combining regimens and dose titration, and adherence to these treatments along with therapeutic lifestyle counseling may facilitate goal attainment.     

Drinking and Driving in Puerto Rico

Background: Epidemiological information is lacking for driving under the influence of alcohol (DUI) in Puerto Rico. Objectives: To examine the prevalence and correlates of DUI in Puerto Rico. Methods: Data are from a household sample of 1510 individuals, aged 18–64 years in San Juan, Puerto Rico. The response rate was 83%. Results: The rate of 12 month self-reported DUI was 20% among men and 8% among women (p < 0.001). Twelve month DUI arrests were reported by 0.1% of men and 0.2% of women (p: ns) while lifetime arrests were reported by 6% of men and 0.7% of women (p < 0.001). Adjusted analyses showed that the number of hours of daily driving (OR = 1.08, 95% CI = 1.01–1.17; p < 0.05), male gender (OR = 1.66, 95% CI = 1.07–2.58; p < 0.01), having more liberal drinking norms (OR = 4.81; 95% CI = 2.61–8.84; p < 0.01) and more positive attitudes towards drinking (OR = 4.58; 95% CI = 1.28–16.31; p < 0.01), consuming a higher number of weekly drinks (OR = 1.05; 95% CI: 1.03–1.07; p < 0.001), and binge drinking (OR = 2.60; 95% CI = 1.62–4.16; p < 0.001) were factors of risk for self-reporting DUI. A lifetime arrest was associated with being separated or divorced (OR = 2.7; 95% CI = 1.04–7.36; p < 0.05), male gender (OR = 5.25; 95% CI = 1.93–14.26; p < 0.001), more liberal drinking norms (OR = 6.97; 95% CI = 2.37–20.48; p < 0.001), and illicit drug use (OR = 2.82; 95% CI = 1.25–6.35; p < 0.001). Conclusions: The prevalence of self-reported DUI in San Juan, Puerto Rico was high, but the proportion of people arrested for DUI in a span of 12 months or during their lifetime was low. Stricter enforcement of DUI laws may be necessary to minimize DUI in urban Puerto Rico.     

Incidence of postoperative residual neuromuscular blockade after general anesthesia: a prospective,multicenter, anesthetist-blind,observational study

Objective:

Evidences demonstrate that postoperative residual neuromuscular blockade (rNMB) is a primary and frequent anesthetic risk factor for postoperative complications. This study was designed to mitigate the paucity of data regarding the occurrence and degree of rNMB in a real-life setting.

Methods:

This prospective, multicenter, anesthetist-blind, observational study enrolled 1571 Chinese adults undergoing elective open or laparoscopic abdominal surgery lasting ≤4 hours from 32 hospitals across China. The patients received anesthesia in accordance with routine practice at the study site. Neuromuscular blockade (NMB) was monitored using acceleromyography, with rNMB defined as a train-of-four (TOF) ratio <0.9.

Results:

The patients’ mean age was 46 years and 71% were female. The procedures included laparoscopic (67%), open abdominal (31%), and laparoscopic to open abdominal (2%). NMB was reversed with neostigmine in 78% of patients. The overall incidence of rNMB at extubation was 57.8%, and the proportions of participant with TOF ratios <0.6, 0.6–0.7, 0.7–0.8, 0.8–0.9 were 22.9%, 6.9%, 11.1% and 16.9%, respectively, immediately prior to endotracheal extubation. Age <45 years (OR?=?0.630, 95% CI?=?0.496–0.801, p?=?0.002), use of one neuromuscular blocking agent (NMBA) (OR?=?0.387, 95% CI?=?0.243–0.618, p?<?0.0001), time from neostigmine administration to endotracheal extubation ≥10?min (OR?=?0.513, 95% CI?=?0.400–0.658, p?<?0.0001) and time from last NMBA administration to endotracheal extubation ≥60?min (OR?=?0.902, 95% CI?=?0.801–0.989, p?=?0411) were correlated with non-rNMB at the time of extubation.

Conclusions:

This observational study demonstrated that the overall incidence of rNMB at the time of endotracheal extubation was high in Chinese patients undergoing abdominal procedures, which necessitates appropriate management in current real-life practice.

Clinical trial registry number:

NCT01871064.     

Healthcare resource utilization of second-generation long-acting injectable antipsychotics in schizophrenia: risperidone versus paliperidone palmitate

Objective: This retrospective longitudinal cohort study aimed to compare treatment patterns, healthcare resource utilization (HRU), and costs in patients with schizophrenia treated with second-generation antipsychotic long-acting injectables (SGA-LAIs): biweekly risperidone LAI versus once-monthly paliperidone palmitate.

Methods: Patients who initiated risperidone LAI or paliperidone palmitate between 1 July 2007 and 31 December 2012 (index date) were identified from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid Multi-State insurance databases. Outcomes were assessed 12 months after the index date. Propensity score matching (1:1) based on patients’ demographics and comorbidities was conducted. Outcome differences between the two cohorts were evaluated using t-tests for continuous variables, chi-square tests for categorical variables, and Wilcoxon rank-sum tests for count and cost variables. Regression models estimated the difference in medication use and adherence, likelihood of HRU, number of HRU events, and healthcare costs when comparing risperidone LAI versus paliperidone palmitate, while further adjusting for patient characteristics and pre-index HRU.

Results: Patient characteristics were well balanced between the two cohorts (n?=?499 each). Significantly lower discontinuation rates (36.5% vs. 53.3%; p?<?0.001) and longer days of LAI coverage (233.6 vs. 131.7 days; p?<?0.001) were observed in the paliperidone palmitate cohort versus the risperidone LAI cohort, respectively. Patients treated with paliperidone palmitate were 12.5 (95% confidence interval [CI]: 9.0–17.8) and 11.7 (95% CI: 8.0–17.4) times more likely to be adherent based on medication possession ratio and proportion of days covered, respectively (p?<?0.001). Patients treated with paliperidone palmitate had reduced likelihood of hospitalization (adjusted odds ratio [95% CI]: 0.72 [0.55–0.95]), fewer emergency department (ED) visits (adjusted incidence rate ratio [aIRR]: 0.67 [0.61–0.73]) and reduced length of inpatient stay (aIRR: 0.86 [0.82–0.90]), which resulted in lower monthly inpatient hospitalization costs (-$77.58; p?=?0.038) and ED visits (-$9.77; p?=?0.021) relative to risperidone LAI.

Limitations: Pharmacy costs were derived from health plan payment in the claims data and do not account for any discounts or rebates. This may have overestimated the branded drug costs in this analysis.

Conclusions: These findings highlight the value of once-monthly paliperidone palmitate in the treatment of patients with schizophrenia.     

Prevalence and economic burden of hyperkalemia in the United States Medicare population

Abstract

Objective: To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population.

Methods: Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010–31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated.

Results: The estimated prevalence of hyperkalemia was 2.6–2.7% in the overall population and 8.9–9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (all p?<?.001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (both p?<?.001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (both p?<?.001).

Conclusions: Hyperkalemia had an estimated prevalence of 2.6–2.7% in the Medicare population and was associated with markedly high healthcare costs.     

Epidemiology and characteristics of emergency departments visits by US adults with psychiatric disorder and antipsychotic mention from 2000 to 2004

ABSTRACT

Background and objective: There is limited research to acquaint clinicians and payers about antipsychotic use in psychiatric patients visiting United States (US) emergency departments (EDs). The study objective is to describe the epidemiology and compare characteristics of ED visits by adults ≥?18 years with psychiatric diagnoses and different types of antipsychotic.

Methods: Data for 2000–2004 adult ED visits were obtained from the National Hospital Ambulatory Medical Care Survey. Sample-weighted national estimates of (1) typical, (2) atypical, or (3) typical–atypical combination antipsychotic-associated psychiatric ED visits with 95% confidence intervals (CIs) were produced. Characteristics of the three psychiatric ED visit groups with antipsychotic mention, (prescribed, supplied, administered, ordered or continued) were analyzed retrospectively. Significant characteristics for atypical versus typical antipsychotic mention at visits were determined using multivariate logistic regression.

Results: Adults made an estimated 26 million ED visits over the 5-year study period that resulted in a psychiatric diagnosis. Of 2 million (or 8%) of these psychiatric ED visits, 38, 55, and 8% mentioned typical, atypical, and combination antipsychotics respectively. From 2000 to 2004 there was an 8-, 3.5-, and 1.5-fold increase in ED visits with combination, atypical, and typical antipsychotics, respectively. The majority of antipsychotic-associated psychiatric ED visits were made by young adults less than 40 years old, Caucasians, needing urgent treatment, and reimbursed by public insurance. More combination-, and typical versus atypical antipsychotic-associated ED visits included a mention of medications for extrapyramidal symptoms (40%, 14% vs. 4%; p < 0.0001) and antianxiety medications (50%, 48% vs. 27%; p < 0.0001). More combination and atypical than typical antipsychotic-related ED visits had anticonvulsant (42%, 35% vs. 12%; p < 0.0001) and antidepressant mentions (31%, 42% vs. 11%; p < 0.0001). A diagnosis of depression (OR 3.2, 95% CI: 1.9–5.3; p < 0.001) or bipolar-disorder (OR 2.5, 95% CI: 1.3–5.0; p = 0.008), and the number of medications received (OR 1.4, 95% CI: 1.0–1.8; p = 0.034) significantly increased the likelihood of atypical versus typical antipsychotic mention at psychiatric ED visits.

Conclusions: Despite limitations of analyses with cross-sectional visit data, an increasing number of combination- and atypical antipsychotic-associated US adult ED visits depict the burden on the healthcare system. The associated characteristics of these visits deserve the attention of providers, and payers for cost-effective patient management.     

Dual Diagnosis and Drinking Behaviors in an Outpatient Treatment Seeking Sample of Adolescents with Alcohol Use Disorders

ABSTRACT

Objectives: Co-occurring psychiatric disorders are common in adolescents with substance abuse. While many studies have explored the prevalence of psychiatric disorders in adolescent substance using samples, few have explored the relationship between comorbid psychiatric disorders and drinking behaviors. This study examined this relationship to investigate whether certain psychiatric disorders impact severity of drinking behaviors in adolescents with alcohol use disorders.

Methods: We examined 34 outpatient adolescents with alcohol use disorders for comorbid psychiatric disorders using the K-SADS. Their drinking behavior patterns were examined using the Time-Line Follow-Back. The alcohol drinking parameters were (1) drinks per drinking day (DDD), (2) percent heavy drinking days (PHD), (3) percent heavy drinking days when drinking (PHDD), and (4) percent days abstinent (PDA).

Results: The diagnoses that afforded sufficient power to examine the effect of that diagnosis on drinking behavior were any mood or anxiety disorder vs. neither; oppositional defiant disorder (ODD) vs. no ODD; and attention-deficit hyperactivity disorder (ADHD) vs. no ADHD. Results revealed no significant effect of either ODD or any mood/anxiety disorder on drinking indices, both p values > .10; MANOVA revealed a significant effect of ADHD diagnosis, p = .04. Univariate analysis showed that for all four drinking indices, the group with ADHD had more severe alcohol use, all p values < .05.

Conclusions: Our results suggest that adolescents with ADHD who meet diagnostic criteria for alcohol use disorders have greater drinking severity than those without ADHD.     

Systematic review and meta-analysis of budesonide/formoterol in a single inhaler

ABSTRACT

Objective: To compare the effectiveness of budesonide/formoterol using fixed dosing (BUD/FORM) with inhaled corticosteroid (ICS) alone or alternative ICS and long-acting β₂-agonist (LABA) regimens for adults with moderate/severe asthma.

Methods: BIOSIS, CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in July 2006. No restriction was placed on language. Meta-analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with BUD/FORM had an equivalent daily dose of ICS at the start of the trial. The primary outcome measure was, ‘treatment failure’, defined as: asthma-related serious adverse event, oral glucocorticosteroid treatment, A&E visit and/or admission to hospital, withdrawal due to a need for additional asthma therapy.

Results: Of the 330 papers identified in the literature search, 15 met the inclusion criteria. The following alternative treatments were found: ICS alone (BUD), BUD/FORM adjustable maintenance dose (BUD/FORM-AMD), and salmeterol/fluticasone in a single inhaler (SALM/FP). Meta-analysis of treatment failure demonstrated a 50% increase with BUD versus BUD/FORM (Relative Risk [RR] 1.50, 95% confidence interval [95% CI]: 1.12–2.02, p = 0.007; 2 RCTs); a trend in favour of a reduction with BUD/FORM-AMD versus BUD/FORM (RR 0.88, 95% CI: 0.77–1.02, p = 0.09; 11 RCTs); and no evidence of a difference with SALM/FP versus BUD/FORM (RR 0.99, 95% CI: 0.83–1.16, p = 0.86; 3 RCTs). Significant heterogeneity was not detected in the primary analyses. Secondary analyses demonstrated the following significant differences: hospitalisations/A&E visits (49% increased risk with SALM/FP vs. BUD/FORM, RR 1.49, 95% CI: 1.07–2.08, p = 0.02, and 28% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.72, 95% CI: 0.52–0.99, p = 0.04); and use of oral steroids (51% increase in risk with BUD vs. BUD/FORM, RR 1.51, 95% CI: 1.10–2.09, p = 0.01, and 19% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.81, 95% CI: 0.70–0.95, p = 0.01).

Conclusions: Fixed-dose BUD/FORM is an effective treatment option for adult patients with moderate/severe asthma when compared to BUD and SALM/FP, with adjustable maintenance dosing demonstrating important advantages over fixed dosing in relation to exacerbation prevention and reduced treatment load.     

The Impact of Pharmacotherapy on Substance Use in Adolescents With Attention-Deficit/Hyperactivity Disorder: Variations Across Subtypes

Objective: The primary purpose of this study was to investigate the impact of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy on the risk of substance use within each ADHD subtype. Methods: The study used data from the National Comorbidity Survey-Adolescent supplement, a nationally representative sample of US adolescents (ages 13–18) collected from 6,483 adolescent-parent interviews conducted between 2001 and 2004. ADHD was categorized into three subtypes: ADHD-predominantly hyperactive-impulsive type (ADHD-H); ADHD-predominantly inattentive type (ADHD-I); and ADHD-combined type (ADHD-C) using Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Substance use information was obtained from the adolescents’ interview. The impact of ADHD-pharmacotherapy on substance use was examined using multivariable logistic regression analysis. Results: Among the adolescents with ADHD, ADHD pharmacotherapy significantly associated with reduced risk of substance use (OR = 0.53, 95%CI [0.31–0.90]); with regards to ADHD subtypes, ADHD pharmacotherapy is negatively associated with substance use in adolescents with ADHD-C (OR = 0.53, 95%CI [0.24–0.97]) and those with ADHD-H (OR = 0.23, 95% CI [0.07–0.78]), but it did not have statistically significant effect on risk of substance use in those with ADHD-I subtype (OR = 0.49, 95%CI [0.17–1.39]). Among the group who never received ADHD-pharmacotherapy before the interview, individuals with ADHD-H and ADHD-C had a similar risk of substance use compared to adolescents with ADHD-I (ADHD-C: OR = 1.5, 95%CI [0.77–2.95] and ADHD-H: OR = 2.10, 95%CI [0.87–4.95]). Conclusions: Adolescents with ADHD were equally susceptible to future substance use disregard their ADHD subtypes. Receipt of pharmacotherapy could decrease risk of substance use in adolescents with ADHD-H and ADHD-C, but it may not affect risk of substance use among individuals with ADHD-I.     

Analgesic efficacy and tolerability of flupirtine vs. tramadol in patients with subacute low back pain: a double-blind multicentre trial

ABSTRACT

Objective: To assess the efficacy and tolerability of flupirtine in comparison with tramadol for the treatment of moderate to severe subacute low back pain (LBP).

Design and methods: In this randomised, double-blind, parallel-group trial, 209 LBP patients, aged 18–65 years, were orally treated with flupirtine 100 mg (n = 105) vs. tramadol 50 mg (n = 104), both three times daily for 5–7days.

Main outcome measures: Patient assessment of pain intensity after 5–7 days (primary); physicians’ global assessment of improvement in pain and functional capacity; adverse events.

Results: Flupirtine showed an overall pain-relieving efficacy comparable to tramadol. Mean LBP intensity after end of treatment dropped from 6.8 (95% CI: 6.5–7.0) to 2.8 (95% CI: 2.3–3.1) for flupirtine and from 6.9 (95% CI: 6.6–7.1) to 3.0 (95% CI: 2.6–3.4) for tramadol, corresponding to pain relief rates of 57% (95% CI: 51–63%) and 56% (95% CI: 50–62%) respectively (p = 0.796), indicating non-inferiority of flupirtine. All other efficacy endpoints supported equivalent efficacy. Adverse events (AEs) occurred significantly less in patients after flupirtine (33%) vs. tramadol (49%) (p = 0.02) and both the respective severity grading and the AE-related dropout rates were significantly lower after flupirtine than after tramadol (1% vs. 15%, p < 0.001).

Conclusion: Flupirtine 100 mg three times daily was associated with a reduction in pain and improvements in functional capacity equivalent to that observed with tramadol 50 mg three times daily, and was better tolerated, when administered to patients with subacute back pain for one week. The limitations of this study were the lack of a placebo control and the short (7-day) duration of the study.     

Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study

SUMMARY

Aims: To estimate the prevalence of vascular disease (coronary heart disease/stroke/peripheral arterial disease) in individuals with the metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) when compared with subjects without the MetSyn.

Patients and methods: A cross-sectional analysis of a representative?sample of Greek adults (n = 4153), men and women (49% and 51%, respectively), living in urban, semi-urban and rural areas (54%, 25% and 21%, respectively). The National Cholesterol Education Program – Adult Treatment Panel III definition of the MetSyn was used.

Results: The age-adjusted prevalence of the MetSyn was 23.6% [95% confidence interval (CI) = 22.4%–25.1%]; this was similar in men and women. The fully adjusted prevalence of vascular disease in those with the MetSyn (n = 984) was 29.4%, significantly higher than in those without (n = 3169, 9.6%, p < 0.0001), while subjects without both the MetSyn and DM had the lowest vascular disease prevalence (n = 3035, 8.9%). Subjects with the MetSyn but no DM (n = 674) had a vascular disease prevalence of 24.1% (?p < 0.0001 vs. those without the MetSyn), which was similar to that in subjects with DM without the MetSyn (n = 134, 25.4%), but lower than in those with both the MetSyn and DM (n = 310, 40.7%, p < 0.0001 vs. all). In comparison to those without the MetSyn [odds ratio (OR) = 1], the ORs of prevalent vascular disease, after multivariate analysis for age, sex and components of the MetSyn, and antiatherosclerotic drugs were: all MetSyn = 1.94 (95% CI = 1.35–2.47), with both MetSyn and DM = 3.04 (95% CI = 1.98–4.11) and with MetSyn but no DM = 1.48 (95% CI = 1.12–1.92).

Conclusions: The prevalence of vascular disease was markedly increased in the presence of the MetSyn. Those with both the MetSyn and DM had the highest prevalence of vascular disease, followed by those with the MetSyn without DM. Probably MetSyn without DM should be considered as a coronary heart disease-risk equivalent in future guidelines. This initiative would reset treatment targets and potentially provide additional benefit in patients with the MetSyn.     

Risk for delirium tremens in patients with alcohol withdrawal syndrome 1

To determine the characteristics associated with an increased risk for delirium tremens (DT) we performed a case‐control study at the detoxification units of two hospitals. Cases met DSM‐IV criteria for DT. For each case (n = 15), 3 controls (n = 45) were chosen. Eligibility criteria were applied equally to cases and controls. Cases were more likely than controls to report a prior complicated withdrawal (DT or alcohol withdrawal seizure) (53 vs. 27%, OR 3.1, 95% CI 0.94–10.55), have a systolic blood pressure greater than 145 mm Hg on admission (60 vs. 27%, OR 4.1, 95% CI 1.21–14.06), and have comorbidity scores of at least 1 (60 vs. 18%, OR 6.9, 95% CI 1.92–25.08). Zero cases (0%) and 15 (33%) controls had no prior complicated withdrawals and no adverse clinical features (systolic blood pressure >145 or comorbidity score >1). Compared to this group, the odds of being a case and having both prior complicated withdrawal and at least 1 adverse clinical feature was 44.8 (95% CI4.36–460). Elevated blood pressure, prior complicated alcohol withdrawal and medical comorbidity, alone and in combination, are associated with an increased risk of delirium tremens.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

Treatment patterns,overall survival,healthcare resource use and costs in elderly Medicare beneficiaries with chronic myeloid leukemia using second-generation tyrosine kinase inhibitors as second-line therapy

Objective Though the median age at diagnosis is 64 years, few studies focus on elderly (≥65 years) patients with chronic myeloid leukemia (CML). This study examines healthcare outcomes among elderly Medicare beneficiaries with CML who started nilotinib or dasatinib after imatinib.

Research design and methods Patients were identified in the Medicare Research Identifiable Files (2006–2012) and had continuous Medicare Parts A, B, and D coverage.

Main outcome measures Treatment patterns, overall survival (OS), monthly healthcare resource utilization and medical costs were measured from the second-line tyrosine kinase inhibitor (TKI) initiation (index date) to end of Medicare coverage.

Results Despite similar adherence, dasatinib patients (N?=?379) were more likely to start on the recommended dose (74% vs. 53%; p?<?0.001), and to have dose reductions (21% vs. 11%, adjusted hazard ratio [HR]?=?1.94; p?=?0.002) or dose increases (9% vs. 7%; adjusted HR?=?1.81; p?=?0.048) than nilotinib patients (N?=?280). Fewer nilotinib patients discontinued (59% vs. 67%; adjusted HR?=?0.80; p?=?0.026) or switched to another TKI (21% vs. 29%; adjusted HR?=?0.72; p?=?0.044) than dasatinib patients. Nilotinib patients had longer median OS (>4.9 years vs. 4.0 years; p?=?0.032) and 37% lower mortality risk than dasatinib patients (adjusted HR?=?0.63; p?=?0.008). Nilotinib patients had 23% fewer inpatient admissions, 30% fewer emergency room visits, 13% fewer outpatient visits (all p?<?0.05), and lower monthly medical costs (by $513, p?=?0.024) than dasatinib patients.

Limitations Lack of clinical assessment (disease phase and response to first-line therapy) and retrospective nature of study (unobservable potential confounding factors, non-randomized treatment choice).

Conclusions In the current study of elderly CML patients, initiation of second-line TKIs frequently occurs at doses lower than the recommended starting doses and, despite this, many patients require dose adjustments. Here, nilotinib patients required fewer dose adjustments than dasatinib patients. Further research focusing on elderly CML patients is warranted in order to help define future best clinical practices.     

Increased healthcare resource utilization in higher disease activity levels in initiators of TNF inhibitors among US rheumatoid arthritis patients

Objective: Determine healthcare resource utilization (HCRU) in biologic-naïve initiators of TNF inhibitors (TNFis) associated with their disease activity from a national cohort of rheumatoid arthritis (RA) patients.

Methods: RA patients were identified at their first TNFi initiation (index date) in the Corrona registry. Patients with age of RA onset <18, comorbid psoriasis/psoriatic arthritis, fibromyalgia, or osteoarthritis were excluded. Patients were categorized into disease activity (DA) strata by the lowest level of DA (and sustaining low levels for at least two visits) using the Clinical Disease Activity Index (CDAI) across all visits in Corrona while on a TNFi during 1 year after initiation. Rates of all-cause and RA-related hospitalizations, rheumatologist visits, and joint surgeries while on TNFi therapy were reported and compared across DA levels along with the incidence rate ratio (IRR) adjusted for age, gender, and RA duration using Poisson mixed models.

Results: Of 1931 RA patients: 15% achieved sustained remission, 22% remission, 14% sustained low DA, 23% low DA and 27% moderate/high DA (M/HDA). Those in M/HDA had statistically higher rates of hospitalizations (37.3 per 100 patient years (py), 95% CI: 31.6–43.7 and joint surgeries (20.8 per 100 py, 95% CI: 16.6–25.8) compared to the sustained remission cohort, resulting in respective IRRs of 2.3 (p?<?0.001) and 1.7 (p?=?0.046).

Conclusion: Many biologic naïve RA patients initiating TNFi failed to achieve sustained remission during a 1 year period while remaining on TNFi therapy. Patients in higher DA levels had higher HCRU rates vs. patients in sustained remission, suggesting that achieving treat-to-target goals would reduce health care expenses.