Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature.

OBJECTIVE: To compile and synthesize the available literature describing medical cannabis use across various disease states. DATA SOURCES: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. DATA SYNTHESIS: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. CONCLUSIONS: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.

Trends in Prevalence of Non-Valvular Atrial Fibrillation and Anticoagulation Therapy in a Japanese Region　- Analysis Using the National Health Insurance Database.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective in reducing thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). However, little is known about trends in NVAF prevalence and DOAC prescriptions in daily clinical practice. This study investigated the current status and trends in NVAF prevalence and DOAC prescriptions in a region of Japan.Methods and Results:Annual data for the 4 years from May 2014 to May 2017 in the Tsugaru region of Aomori Prefecture, Japan, were obtained for analysis from the Japanese National Health Insurance database ("Kokuho" database [KDB]). The prevalence of NVAF in subjects aged 40-74 years increased gradually over the 4-year study period (1,094/57,452 [1.90%] in 2014, 1,055/56,018 [1.88%] in 2015, 1,072/54,256 [1.98%] in 2016, and 1,154/52,341 [2.20%] in 2017). The proportion of NVAF patients prescribed warfarin decreased (42%, 33%, 24%, and 21% in 2014, 2015, 2016, and 2017, respectively), the proportion of those prescribed DOACs increased (30%, 42%, 50%, and 57%, respectively), and the proportion not prescribed an oral anticoagulant (OAC) decreased (28%, 25%, 26%, and 22%, respectively). However, 17% of patients with a CHADS2score ≥2 were not prescribed an OAC in 2017. CONCLUSIONS: By using the KDB we found that the prevalence of NVAF has increased gradually from 2014 to 2017. In the Tsugaru region in Japan, DOACs prescriptions increased and warfarin prescriptions decreased over the 4-year period.

Use of attention-deficit/hyperactivity disorder medication among older adults in Denmark.

AIMS: Knowledge on the use of attention-deficit/hyperactivity disorder (ADHD) medication among older adults is limited. We hypothesized that ADHD medication is used off-label in adults aged ≥50 years as part of palliative care in e.g. cancer patients. The aim of this study was to describe the use of ADHD medication among adults aged ≥50 years in Denmark. METHODS: Using the Danish health registries, we identified new users ≥50 years of ADHD medication during 2000-2012. We estimated the annual incidence of ADHD medication use and ADHD diagnoses. We described new users of ADHD medication according to co-medication, comorbidities and assessed the 1-year cumulative mortality rate. A posthoc analysis allowed us to include new users until 2015. RESULTS: We identified 6690 new users of ADHD medication from 2000 to 2012. From 2000 to 2015 we observed an increase in the incidence of ADHD medication use from 12.5 to 30.3 per 100 000 person-years. However, the incidence rate decreased from 2010 to 2015. Throughout the study period, the incidence rate of ADHD diagnoses was low (overall prevalence among new users ≤2%). Opioids were the most frequent comedication used (used by 54%), while cancer was the most frequent diagnosis preceding treatment (prevalence of 52%). The 1-year cumulative mortality was 50%, primarily driven by patients with a preceding cancer diagnosis. CONCLUSION: There was an increase in the incidence of ADHD medication use in adults aged ≥50 years from 2000-2010 and a decreasing incidence from 2010-2015. Our results suggest that ADHD medication is used off-label in older adults as part of palliative care.

Evaluation of pegfilgrastim use at an academic medical center.

PURPOSE: Pegfilgrastim is indicated to reduce the risk of febrile neutropenia. As a cost-savings initiative, Pegfilgrastim Process Guidelines were developed and implemented at a large, academic teaching institution to improve appropriate use of pegfilgrastim and to decrease costs of outpatient infusion center administration by deferring doses to home self-administration for eligible patients. METHODS: A retrospective medical record review was conducted post-implementation of the Pegfilgrastim Process Guideline to evaluate the use of pegfilgrastim and to assess the safety and efficacy of transferring pegfilgrastim orders from outpatient infusion center to home administration for eligible patients. RESULTS: Fifty-nine patients were included in the study, with 35 patients receiving pegfilgrastim in the outpatient infusion center, 13 patients self-injecting at home, and 11 patients receiving doses in both settings. The total wholesale cost avoidance for pegfilgrastim orders transferred to self-administration at home during this time period totaled $205,163. The revenue from outpatient prescriptions of pegfilgrastim totaled $291,111.93. The percentage of febrile neutropenia admissions was 11.4%, 0%, and 9.1% in the outpatient infusion, home, and outpatient/home group, respectively. CONCLUSION: Implementation of the Pegfilgrastim Process Guidelines demonstrated decreased total pegfilgrastim orders to be dispensed by the infusion center and a cost avoidance of $205,163 in four months without any perceivable changes in patient outcomes. This represents a significant cost-savings opportunity.

Analgesic Drug Prescription After Carpal Tunnel Surgery: A Pharmacoepidemiological Study Investigating Postoperative Pain.

BACKGROUND AND OBJECTIVES: Carpal tunnel syndrome is a frequent cause of neuropathic pain of the upper limb. Surgery is often proposed in second-line treatment, leading to an expected decrease in analgesic drug consumption. The main objective of this study was to investigate the variations in analgesic drug prescriptions, with a special focus on constant or increasing prescription patterns, before and after surgery for carpal tunnel syndrome. METHODS: We designed a retrospective cohort study of French beneficiaries from the health insurance system in Midi-Pyrénées area. All patients undergoing carpel tunnel surgery during a specified period were identified and included. Definition of increased or constant prescription of analgesics was based on the comparison of the accumulated defined daily doses received by months and a difference between early preoperative (2 months before) and late postoperative period (2-12 months after surgery) superior to a -3.5 margin. We performed 4 multivariate logistic regression models to identify factors associated with increased or constant analgesic drug prescription patterns (for all analgesics, opioid, antineuropathic, nonopioid drugs). RESULTS: Among the 3665 patients included, 3255 (89%) received at least 1 analgesic drug during the late postoperative period (39% [n = 1426] for opioids and 15% [n = 563] for antineuropathic drugs). Prescription of analgesic, opioid, or antineuropathic drugs was maintained or increased in the late postoperative period in 11%, 5%, and 3% of the population, respectively. High levels of preoperative pain and female sex were associated with an increase in opioid use, whereas inpatient surgery (vs ambulatory surgery), high levels of preoperative pain, and psychiatric disorders were found to be associated with an increase in antineuropathic drug use. CONCLUSIONS: This study revealed that approximately 3% to 5% of patients undergoing carpal tunnel surgery had persistent and even increased use of opioid or antineuropathic drugs more than 2 months after surgery, in relation with possible chronic postoperative pain. Considering the incidence of carpal tunnel syndrome, the risks associated with persistent opioid use in this population should be further monitored.

Irrational antibiotic prescribing practice among children in critical care of tertiary hospitals.

This study assessed the prescribing pattern of irrational use of antibiotic among children under age of 12 years in public and private sector hospitals in Pakistan. The prospective clinical evaluation of drug utilization pattern of antimicrobials from Patient Bedside File (PBF) of in-patients and Culture Sensitivity Test (CST) reports were evaluated to determine the antibiotic resistance. Two indicators recorded to assess antibiotic prescribing were; dose of prescribed antibiotic (low-dose, rational and high -dose) and Indication (valid or invalid). Antibiotics resistance for 25 selected antibiotics was determined by culture sensitivity test. This study showed that in Private Sector Hospital 77.7% neonates, 13.3% infants and 9% children admitted in ICU were receiving antibiotics, among them only 57.3% neonates, 62% infants and 59.9% children were found valid that is prescribed antibiotics for right indication. 27% neonates, 19% infants and 22.1% children were prescribed under dose of antibiotics, which may lead to antimicrobial resistance and increased cost of hospital stay. Only 29.1% neonates, 30% infants and 36.8% children were receiving rational dosing. In Public Sector Hospital, 65.6% neonates, 19.4% infants and 15% children were receiving antibiotics. Among them valid indication was found in 35.3% neonates, 35.6% infants and 39.8% in children. 33.3% neonates, 26.6% infants and 28.2% children were receiving under dose that may lead to resistance not only among those who were prescribed under dose but also such bacteria become resistant and spread to other population to increase antimicrobial resistance. The irrational prescribing of antibiotics was found very high (above 50%) in Public sector hospital (Hospital-B) for every age group whereas in Private sector hospital (Hospital-A) this practice was found near to 50%. In this study the prescribing frequency of Amikacin, Cefixime, Cefotaxime, Meropenem, Amoxicillin, Vancomycin, Azithromycin, Levofloxacin and Clarithromycin was found above 80% in both hospitals (A and B). Among these, Amoxicillin, Penicillin, Erythromycin and Cephalexin showed higher resistance i.e. 49.2%.

Contemporary Time Trends in Use of Antiplatelet Agents Among Patients with Acute Coronary Syndrome and Comorbid Diabetes Mellitus or Chronic Kidney Disease.

STUDY OBJECTIVE: To describe contemporary trends of P2Y12 inhibitor use in patients with acute coronary syndrome (ACS) and comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD) who have a higher risk of recurring ACS and may benefit from treatment with higher efficacy third-generation agents (prasugrel and ticagrelor). DESIGN: Observational cohort study. SETTING: A large U.S. commercial insurance program (2009-2015). PATIENTS: P2Y12 inhibitor initiated within 2 weeks after an ACS event. MEASUREMENTS AND MAIN RESULTS: We identified 98,649 P2Y12 inhibitor initiators, of whom 24.5% had comorbid DM (no CKD), 10.5% had CKD (no DM), and 12.6% had DM and CKD. Overall, 85.2% of patients initiated clopidogrel, followed by prasugrel (11.6%) and ticagrelor (3.2%). Prasugrel use decreased over time irrespective of preexisting DM and/or CKD; ticagrelor use increased. In logistic regression models accounting for patient demographics and clinical covariates, preexisting DM alone was not associated with prasugrel or ticagrelor versus clopidogrel treatment initiation; however, having CKD with or without DM significantly reduced the likelihood of receiving prasugrel versus clopidogrel (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.74-0.88 for CKD alone; OR 0.91, 95% CI 0.83-0.98 for DM and CKD). Comorbid DM and CKD reduced the odds of initiating ticagrelor versus clopidogrel (OR 0.80, 95% CI 0.70-0.92). PRINCIPAL CONCLUSIONS: We observed lower or similar use of prasugrel and ticagrelor compared with clopidogrel in patients with ACS and comorbid DM and/or CKD. Given the potential for worse clinical outcomes with clopidogrel in these patients, our findings highlight the need to investigate the implications of these trends on recurrent ACS and bleeding events.

Evaluation of medication use in Malaysian predialysis patients.

Chronic kidney disease (CKD) patients suffer from multiple comorbidities and complications as a cause or consequence of kidney disease. Information regarding medication- prescribing patterns in predialysis patients is sparse. We conducted a retrospective study to evaluate the medication prescription patterns among predialysis patients. Medical records (both paper based and computerized) of patients at CKD Resource Centre, Hospital Universiti Sains Malaysia, were reviewed. A total of 615 eligible cases were included in the study. The mean number of medications prescribed per patient was 8.22 ± 2.81, and medication use was correlated to the renal function (stage 3a < stage 3b < stage 4 < stage 5; P <0.001). The top three prescribed medication groups were found to be lipid-lowering agents, calcium channel blockers, and antiplatelet agents. Some medication classes such as nonaluminum/noncalcium phosphate binders, erythropoietin-stimulating agents, and renin-angiotensin-aldosterone system blockers, particularly in advanced stage, were found to be underutilized. In conclusion, predialysis patients are prescribed a large number of medications. Our findings highlight the need for assessing the impact of current medication-prescribing patterns on morbidity and mortality rates in Malaysian predialysis population.

A medication review and deprescribing method for hospitalised older patients receiving multiple medications.

BACKGROUND: Prescribing of multiple medications in older patients poses risk of adverse drug events. AIM: To determine whether a structured approach to deprescribing - identifying and discontinuing unnecessary medications - in the inpatient setting is feasible and reduces medication burden. METHODS: Prospective pilot study of a convenience sample of patients aged ≥65 years admitted acutely to general medicine units in a tertiary hospital and receiving eight or more regular medications on presentation. The intervention comprised an education programme and a paper-based or computerised proforma listing clinical and medication data linked with a five-step decision support tool for selecting drugs eligible for discontinuation, which were then ceased or were being weaned by the time of discharge. RESULTS: Among 50 patients of median age 82.5 years and six co-morbidities, 186 of 542 (34.3%) regular medications were discontinued, representing a significant decrease in the median (interquartile range) number of medications per patient at discharge compared with presentation (7 (5-9) vs 10 (9-12), P < 0.001). Medication lists were reduced by at least two medications in 84% of patients, and by four or more in 50%. Statins, gastric acid suppressive agents, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists and inhaled bronchodilators were the most frequently ceased medications. Of 39 patients in whom follow-up status at a median of 78 days was ascertained, only 5 of 413 (1.2%) ceased medications were recommenced among three patients because of symptom relapse. CONCLUSION: A standardised method of medication review and deprescribing may significantly reduce medication burden in a cohort of older hospitalised patients.

Patterns of androgen deprivation therapies among men diagnosed with localised prostate cancer: a population-based study.

AIM: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. METHODS AND MATERIALS: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. RESULTS: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0-12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. CONCLUSION: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment.

Prevalence and patterns of antipsychotic use in youth at the time of admission and discharge from an inpatient psychiatric facility.

The objective of this study was to examine the prevalence and patterns of antipsychotic use in children and adolescents at the time of admission and discharge from a tertiary care inpatient psychiatric facility. This retrospective analysis included all patients 18 years and younger, who were admitted and discharged from a child and adolescent tertiary care inpatient psychiatric facility between May 1, 2008 and December 31, 2009. Data for medications at admission were obtained using a province-wide network that links all pharmacies in British Columbia, Canada to a central set of data systems, whereas data for medications at discharge were obtained using the Department of Pharmacy's (British Columbia Children's Hospital, Vancouver, British Columbia, Canada) inpatient computer database. Apart from antipsychotics, overall drug use included antidepressants, mood stabilizers, benzodiazepines, anticholinergics, stimulants, and sleep medications. Referral and discharge diagnoses were also examined. During the study period, 335 patients were admitted and discharged from the tertiary care inpatient psychiatric facility. Significantly, more patients were prescribed with an antipsychotic at the time of discharge from hospital compared with that of the time when they were admitted to hospital (51.6% vs 30.7%; P < 0.0001). Antidepressants were most often coprescribed with an antipsychotic at admission and discharge (32.0% vs 42.2%, respectively) followed by attention-deficit/hyperactivity disorder medications (22.3% vs 24.9% at admission and discharge, respectively) and anticonvulsants (19.4% vs 19.1% at admission and discharge, respectively). Whether the significant increase in antipsychotic use seen from the time of admission to discharge is solely attributed to clinical worsening or other variables requires further investigation.

Epidemiological trends in the utilization of bone morphogenetic protein in spinal fusions from 2002 to 2011.

STUDY DESIGN: Retrospective database analysis. OBJECTIVE: A nationwide population-based database was analyzed to assess the utilization trends of bone morphogenetic protein (BMP) in spine fusion surgery from 2002-2011. SUMMARY OF BACKGROUND DATA: The utilization of off-label BMP in spine procedures is not well characterized. The purpose of this study was to analyze a population-based database to characterize the national trends of BMP utilization in terms of incidence, demographics, costs, and mortality. METHODS: Data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project was queried for each year from 2002-2011. Patients undergoing an anterior cervical fusion or posterior cervical fusion, anterior lumbar fusion or posterior lumbar fusion, or a posterior thoracic fusion were identified and separated into cohorts. The frequency of BMP utilization was assessed in each surgical cohort by year. Patient demographics, hospital parameters, costs, and mortality rates were assessed. RESULTS: The adjusted annual number of procedures with BMP increased from 1116 in 2002 to 79,294 in 2011 (P < 0.001), representing 26.9% of all spinal fusion procedures. The rate of BMP utilization within each surgical cohort also significantly increased during the 10-year period (P < 0.001). The posterior lumbar fusion cohort accounted for the majority of spinal fusions that used BMP, representing 76.8% of all spinal fusions between 2002 and 2011. The anterior lumbar fusion cohort was associated with the highest proportion of BMP utilization, peaking at 56.9% of all anterior lumbar interbody fusions in 2006. The trend of BMP utilization in the anterior cervical fusion cohort peaked in 2007 with 10.6% of cases and then declined to 6.4% in 2011. There was a statistically significant trend of older patients with increasing comorbidities receiving BMP during this period. Hospital costs (adjusted for inflation) significantly increased an average of $9560 from 2002-2010. There were no significant trends with regard to the length of hospitalization stay and mortality rates during this period. CONCLUSION: This nonconflicted study demonstrates that the utilization of BMP has dramatically increased from 2002-2011. Interestingly, off-label application of BMP accounts for the vast majority of BMP utilization. The increase in the total hospital costs is likely multifactorial; older patients with more comorbidities undergoing surgery as well as the increasing utilization of BMP are all likely contributory factors. The length of hospitalization stay and mortality rates did not increase during the 10-year period.

Socioeconomic deprivation does not affect prescribing of secondary prevention in patients with peripheral arterial disease.

AIM: Aim of the study was to assess the effect of socioeconomic deprivation on prescribing of cardiovascular secondary prevention medications in patients referred with peripheral arterial disease (PAD). METHODS: A retrospective review of vascular clinic referrals was performed. All patients referred from primary care with suspected PAD over a two month period were included. The deprivation score, prescription of cardiovascular secondary prevention medications, smoking status and the presence of cardiovascular co-morbidities (coronary artery or cerebrovascular disease--CAD/CVD) were assessed. Comparison was made between socioeconomic groups using the Carstairs Deprivation (DepCat) Score and between patients with and without a history of currently existing cardiovascular co-morbidities. RESULTS: The study included 391 patients. Almost two thirds of patients (253) were from the most deprived socioeconomic groups and were significantly younger at presentation (median age DepCat 7: 63 yrs, DepCat 1-2: 74.5 yrs, P<0.0001). The majority of patients with a prior history of CAD/CVD were prescribed secondary preventative medications at the time of referral with suspected PAD whereas those with no prior history of CAD/CVD, (212 patients, 54%) were significantly less likely to be prescribed antiplatelets (47% vs. 83%), statins (45% vs. 86%) or ACEi/ARBs (29% vs. 68%) (all P<0.05). Secondary prevention prescribing did not differ between socioeconomic groups. CONCLUSION: Secondary prevention prescribing is inadequate in patients with suspected PAD regardless of socioeconomic group and is significantly lower in those without previously diagnosed CAD/CVD. There remains a lack of appreciation of the high cardiovascular risk associated with PAD.

Management of lower urinary tract symptoms related to benign prostatic hyperplasia in real-life practice in france: a comprehensive population study.

BACKGROUND: Male lower urinary tract symptoms (LUTS) are one of the most treated diseases, but little is known about patient trajectories in current clinical practice. OBJECTIVE: To describe the dynamic treatment patterns of LUTS presumably due to benign prostatic obstruction (BPO). DESIGN, SETTINGS, AND PARTICIPANTS: All prescriptions of α1-adrenergic receptor blocking agents (α1-blockers), 5α-reductase inhibitors (5-ARIs), and phytotherapy, and all surgeries related to BPO performed in France from 2004 to 2008 were identified using two distinct administrative claim databases maintained by the National Health Insurance system that covers the entire population. After linking the two data sets, all consecutive treatment events were analyzed for each patient. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescription details were assessed for each year, region, and prescriber qualification. Medical treatment initiation, interruption, evolution, and events after surgical management (hospital stay, reoperation, complication rates, and subsequent medical prescriptions) were also investigated. RESULTS AND LIMITATIONS: Overall, 2 620 269 patients were treated within 5 yr, with important geographic variations. Medical treatment was interrupted for approximately 16% of patients. The α1-blockers were prescribed most frequently, but phytotherapy surprisingly accounted for 27% of all monotherapies and 54% of all combination therapies. General practitioners and urologists (92% and 3.7% of overall prescribers, respectively) exhibited a similar prescription profile. Treatment initiation was medical in 95.4% of cases, consisting primarily of monotherapy using α1-blockers (60.3%), phytotherapy (31.8%), or 5-ARIs (7.9%). Treatment was modified at extremely high rates within 12 mo of initiation (8.7%, 14.6%, and 12.9%, respectively). The median hospital stay for surgical management was far higher than in clinical trials. Long-term surgical complications and reoperation rates favored open prostatectomy. Incidence of pharmacologic treatment after surgery was as high as 13.8% at 12 mo. CONCLUSIONS: This unique dynamic evaluation of clinical practice revealed unexpected results that contrast with previously published evidence from clinical trials. This approach may merit monitored and targeted measures to improve the level of care in the field.

Secondary medical prevention after primary vascular surgery between 1996 and 2006: a shift towards more evidence-based treatment.

OBJECTIVE: The implementation of evidence-based secondary medical prevention in peripheral arterial disease (PAD) patients has received increasing attention in recent years, but population-based data are sparse. This study examined the use of secondary medical prophylaxis in unselected symptomatic PAD patients in Denmark. DESIGN: A nationwide follow-up study based on individual-level record linkages of population-based healthcare registers was performed. PARTICIPANTS: All patients who underwent primary vascular reconstruction in Denmark between 1996 and 2006 with a minimum of 6 months of follow-up were included (n = 16,492). METHODS: Data were obtained from prescriptions that were filled six months after primary vascular reconstruction (±90 days). The use of secondary medical prevention was examined according to calendar year and place of residence. RESULTS: The use of lipid-lowering drugs increased from 32.2% in 1996 to 76.1% in 2006 (adjusted relative risk (RR) 1.95, 95% CI 1.81-2.10). The overall use of antihypertensive therapy was unchanged during the study period, but treatment shifted from diuretics/calcium antagonists towards angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. The use of combination therapy (concomitant lipid-lowering, antiplatelet and any antihypertensive therapies) increased from 29.1% in 1996 to 67.6% in 2006 (adjusted RR 1.95, 95% CI 1.80-2.12). This shift in the use of secondary medical prevention was independent of sociodemographic and clinical factors. No substantial differences in pharmacological use based on place of residence were observed. CONCLUSION: The use of evidence-based secondary medical prevention, especially lipid-lowering drugs, increased substantially among symptomatic PAD patients in Denmark from 1996 to 2006. However, recommendations in current clinical guidelines suggest that room for improvement remains.

Cost burden and treatment patterns associated with management of heavy menstrual bleeding.

OBJECTIVES: This study evaluated the healthcare resource use, work productivity loss, costs, and treatment patterns associated with newly diagnosed idiopathic heavy menstrual bleeding (HMB) using a large employer database. METHODS: Medical and pharmacy claims (1998-2009) from 55 self-insured U.S. companies were analyzed. Women aged 18-52 years with ≥2 HMB claims (ICD-9 626.2, 627.0) and continuously enrolled for ≥6 months before the first claim were matched 1:1 with controls. Exclusion criteria were cancer, pregnancy, and infertility; HMB-related uterine conditions; endometrial ablation; hysterectomy; anticoagulant medications; and other known HMB causes. All-cause healthcare resource use and costs were compared between the HMB and control cohorts using statistical methods accounting for matched study design. Treatment patterns were examined for HMB subjects. RESULTS: HMB and control cohorts (n=29,842 in both) were matched and balanced in baseline characteristics and costs. During follow-up, HMB subjects had significantly higher all-cause resource use than did control subjects: hospitalization incidence rate ratio (IRR)=2.70 (95% confidence interval [CI] 2.62-2.79); emergency room visits IRR=1.35 (95% CI 1.31-1.38); outpatient visits IRR=1.29 (95% CI 1.29-1.30). Average annualized all-cause costs were also higher for HMB subjects than controls (mean difference $2,607, p<0.001). Costs associated with HMB claims represented 50% ($1,313) of the all-cause cost difference. Of HMB subjects, 63.2% underwent surgical treatment as initial therapy. CONCLUSIONS: In this large matched-cohort study, an idiopathic diagnosis of HMB was associated with high rates of surgical intervention and increased healthcare resource use and costs.

Trends in use of high-risk medications for older veterans: 2004 to 2006.

OBJECTIVES: To examine the change in use of high-risk medications for the elderly (HRME), as defined by the National Committee on Quality Assurance's Healthcare Effectiveness Data and Information Set (HEDIS) quality measure (HEDIS HRME), by older outpatient veterans over a 3-year period and to identify risk factors for HEDIS HRME exposure overall and for the most commonly used drug classes. DESIGN: Longitudinal retrospective database analysis. SETTING: Outpatient clinics within the Department of Veterans Affairs (VA). PARTICIPANTS: Veterans aged 65 by October 1, 2003, and who received VA care at least once each year until September 30, 2006. MEASUREMENTS: Rates of use of HEDIS HRME overall and according to specific drug classes each year from fiscal year 2004 (FY04) to FY06. RESULTS: In a cohort of 1,567,467, high-risk medication exposure fell from 13.1% to 12.3% between FY04 and FY06 (P<.001). High-risk antihistamines (e.g., diphenhydramine), opioid analgesics (e.g., propoxyphene), skeletal muscle relaxants (e.g., cyclobenzaprine), psychotropics (e.g., long half-life benzodiazepines), endocrine (e.g., estrogen), and cardiac medications (e.g., short-acting nifedipine) had modest but statistically significant (P<.001) reductions (range -3.8% to -16.0%); nitrofurantoin demonstrated a statistically significant increase (+36.5%; P<.001). Overall HEDIS HRME exposure was more likely for men, Hispanics, those receiving more medications, those with psychiatric comorbidity, and those without prior geriatric care. Exposure was lower for individuals exempt from copayment. Similar associations were seen between ethnicity, polypharmacy, psychiatric comorbidity, access-to-care factors, and use of individual HEDIS HRME classes. CONCLUSION: HEDIS HRME drug exposure decreased slightly in an integrated healthcare system. Risk factors for exposure were not consistent across drug groups. Future studies should examine whether interventions to further reduce HEDIS HRME use improve health outcomes.

Knowledge of the pharmacological profile of a patient improves the quality of prescribing, the outcomes of treatment, and the utilization of health services in primary health care.

PURPOSE: To evaluate the influence of the pharmacological profile of a patient (PPP) on quality of drug prescribing, treatment effectiveness, safety, and health services utilization in a group of outpatients. METHODS: The study was designed as an open, nonrandomized trial of an intervention in health care. The outpatient intervention group (n = 39) received the PPP, and the control group (n = 36) did not. In all cases, the outcomes were observed for a 2-year period in total; in the intervention group 1 year of observation was allocated before and another year after the introduction of the PPP. RESULTS: The PPPs reduced multiple prescriptions by 1.08 ± 1.13 drugs per patient, whereas in those who did not receive the PPP, an increase of 1.44 ± 1.48 drugs per patient occurred (P < 0.001, 95% CI 1.91-3.13). A decrease in the medication appropriateness index score of 0.81 ± 0.51 per drug per patient in the intervention group was observed (P = 0.001, 95% CI 0.63-0.93), and in the control group an increase was noted (0.13 ± 0.40; P = 0.063). The majority of patients with PPP experienced fewer adverse drug reactions (0.96 ± 0.58 fewer, P < 0.001 vs. controls, 95% CI 1.39-2.13), and they were more likely to have an improvement in health status (OR 22.0, 95% CI 5.87-82.41). Finally, the PPPs decreased both the number of examinations and the number of diagnostic investigations, on average by 2.15 and 2.26 services per patient, respectively. CONCLUSIONS: Use of a pharmacological profile of a patient in primary care practice could improve not only prescribing behavior of general practitioners, but also effectiveness and safety of therapy, while reducing utilization of health services.

Prevalence of potentially inappropriate prescribing in an acutely ill population of older patients admitted to six European hospitals.

PURPOSE: Potentially inappropriate prescribing is common in older people presenting to hospital with acute illness in Ireland. The aim of this study was to determine if this phenomenon is unique to Ireland or whether it is a more widespread problem in hospitals across Europe. METHODS: Prospective data were collected from 900 consecutive older patients admitted to six university teaching hospitals (150 patients per centre) in Geneva (Switzerland), Madrid (Spain), Oostende (Belgium), Perugia (Italy), Prague (Czech Republic) and Cork (Ireland). Age, gender, comorbidity, cognitive status, prescription medicines taken before admission and baseline haematological, biochemical and electrocardiographic data were recorded. STOPP and Beers' criteria were applied to detect potentially inappropriate medicines (PIMs). START criteria were applied to detect potentially inappropriate prescribing omissions (PPOs). RESULTS: The overall PIM prevalence rate was 51.3% using STOPP criteria, varying from 34.7% in Prague to 77.3% in Geneva, and 30.4% using Beer's criteria, varying from 22.7% in Prague to 43.3% in Geneva. Using START criteria, the overall PPO prevalence rate was 59.4%, ranging from 51.3% in Cork to 72.7% in Perugia. Polypharmacy predicted the presence of PIMs using STOPP criteria [with >10 medications: odds ratio (OR) 7.22, 95% confidence interval (CI) 4.30-12.12, p < 0.001] and Beers' criteria (with >10 medications: OR 4.87, 95% CI 3.00-7.90, p < 0.001). Increasing co-morbidity (Charlson Index ≥2) and age ≥85 years significantly predicted PPOs. CONCLUSION: Potentially inappropriate drug prescribing and the omission of beneficial drugs are highly prevalent in acutely ill hospitalized older people in six European centres.

Impact of erythropoiesis-stimulating agent prescribing at an Asian cancer center, after release of safety advisories.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) provide symptom relief and decrease blood transfusion support among patients with chemotherapy-induced anemia. However, due to increased cardiovascular events associated with off-labeled usage of ESAs, the FDA incorporated black box warnings in 2007 to include the following key points: (a) ESAs should be used only to treat anemia due to concomitant chemotherapy of a noncurative intent and (b) target hemogloblin level should not exceed 12 g/dL. Thus, this study was designed to compare the prescribing of epoetin alfa at National Cancer Centre Singapore before and after FDA black box updates. The secondary objective of this study was to evaluate the appropriateness of efficacy and toxicity monitoring of epoetin alfa. METHODS: This was a retrospective, single-centered, drug utilization review. Patients who received at least one dose of epoetin alfa were included in this study. Utilization of epoetin alfa was segregated into two time periods: January 1, 2005 to October 15, 2007 (S1, Pre-safety advisories changes) and October 16, 2007 to December 10, 2009 (S2, Post-safety advisories changes). RESULTS: A total of 171 patients were prescribed epoetin alfa at NCCS during the two time periods. However, only 139 patients were eligible for analysis, with 91 and 48 patients in S1 and S2 respectively. After safety advisory changes, there were more (18.2%) metastatic patients and fewer (19.1%) patients with cardiovascular co-morbidities who were prescribed epoetin alfa, the mean hemogloblin level when epoetin alfa was initiated was lowered by 0.46 g/dL, more (43%) dose adjustments were made for 'excessive' responders and more (40.7%) patients had fewer blood transfusions after epoetin alfa therapy (p < 0.05). However, blood pressure control, iron studies, and supplementation did not improve (p > 0.05). CONCLUSION: This study suggested that oncologists have generally adopted the new ESA safety warnings and adjusted prescribing habits.