Measurement properties of the benign prostatic hyperplasia impact index in tadalafil studies.

BACKGROUND: To assess the measurement properties of the Benign Prostatic Hyperplasia Impact Index (BII) for use in men with Lower Urinary Tract Symptoms (LUTS) secondary to Benign Prostatic Hyperplasia (BPH) treated with tadalafil. METHODS: Data from a dose-titration (Study 1) and a dose-finding placebo-controlled (Study 2) tadalafil studies of men 45 years of age or older with moderate to severe LUTS (N = 281; N = 1053) were included in this post-hoc analysis. Measures included the BII, International Prostate Symptom Score (IPSS), IPSS Quality of Life Index (IPSS-QoL), LUTS Global Assessment Question, uroflowmetry measure peak flow rate (Qmax) and postvoid residual volume (PVR). Spearman rank and Pearson correlation coefficients were computed between the BII score and the other measures at each visit. Wilcoxin two-sample tests, t-tests and general linear modeling compared BII scores of subjects with global ratings of improvement versus no improvement, and subjects taking tadalafil versus placebo. Effect size, standardized response mean and Guyatt's responsiveness statistic were calculated for BII and IPSS change scores. RESULTS: There were high correlations between BII and IPSS & IPSS-QoL and low correlations between BII and Qmax & PVR at each visit. There were significant differences in BII at the End-of-Study Visit between subjects reporting improvement versus subjects reporting no improvement (Studies 1 and 2, P < .0001) and subjects taking tadalafil versus subjects taking placebo (Study 1, P = .0045; Study 2, P = .0064). The BII and IPSS were both responsive to change. CONCLUSIONS: Results show that the BII is reliable, shows responsiveness to change in patients with BPH-LUTS, and demonstrates construct validity.

Impact of drug use and comorbidities on in-hospital falls in patients with chronic kidney disease.

BACKGROUND: In-hospital falls are a major problem in healthcare institutions and contribute to morbidity and mortality in this setting. Patients with chronic kidney disease (CKD) were previously found to be at higher risk for experiencing an in-hospital fall. OBJECTIVE: To evaluate the association between comorbidities and drug use with the risk of in-hospital falls in adults with CKD. METHODS: A retrospective case-control study was conducted in patients with CKD hospitalized between January 1, 1998, and June 30, 2003. Cases included patients who experienced an in-hospital fall, were 18 years of age or older, and had been hospitalized for more than 24 hours. For every case, 2 controls were identified and matched for CKD, age, and sex. Information about comorbidities and drug use was collected from an electronic medical data repository. Statistical tests performed were t-tests, chi2 analysis, and multivariate logistic regression, using occurrence of a fall as the dependent variable and race, comorbidities, and drug groups as covariates. RESULTS: There were 635 fall cases that met study criteria. The mean age of patients was 68 +/- 15 years, 54% were female, and 82% were white. There were 1270 matched controls with CKD who were included in the regression analysis. Comorbidities that increased the likelihood of experiencing an in-hospital fall were dementia (OR 2.63), pneumonia (OR 1.72), gastrointestinal disease (OR 1.41), and diabetes (OR 1.31). Drugs associated with an in-hospital fall were antidepressants (OR 1.65) and anticonvulsants (OR 1.52). CONCLUSIONS: Several comorbidities, especially dementia, significantly increase the risk of experiencing an in-hospital fall in patients with CKD. Drugs that place CKD patients at risk include antidepressants and anticonvulsants.

Children's acetaminophen exposures reported to a regional poison control center.

PURPOSE: The patient characteristics, doses taken, and types of exposures in children with acetaminophen-related exposures reported to a regional poison control center (RPCC) were studied. METHODS: A retrospective review was conducted of all acetaminophen exposures that occurred between October 31, 2000, and October 31, 2003, in children younger than 18 years who were managed by an RPCC. Children were grouped into three age categories: less than 6 years (group 1), 6-12 years (group 2), and 13-17 years (group 3). Data collected included patient demographics, drug details, type of exposure, time since exposure, exposure site, and caller site. RESULTS: There were 473 exposures to acetaminophen: 76% in group 1, 3% in group 2, and 21% in group 3. Sex was distributed equally among groups, except group 3 was 83% females. The majority of callers seeking information on acetaminophen ingestion in children younger than 12 years were family members (62%), whereas health professionals (61%) were the most common callers for children over 12 years. Unintentional ingestion was the most common type of exposure in group 1 (100%) and group 2 (93.7%). In group 3, intentional ingestions were more common (91%), with females representing far more of these exposures than males (87% versus 14%, respectively). Acetaminophen doses over 200 mg/kg were ingested by 47% of children in group 3. CONCLUSION: Most acetaminophen exposures reported to an RPCC occurred in children less than six years of age and were unintentional, whereas exposures in children over 12 years were more likely to be intentional overdoses.

The translation and cultural adaptation of the Child Behavior Checklist for use in Israel (Hebrew), Korea, the US (Spanish), India (Malayalam and Kannada), and Spain.

BACKGROUND: The Child Behavior Checklist (CBCL) is a caregiver rating scale for assessing the behavioral profile of children. It was developed in the US, and has been extensively translated and used in a large number of studies internationally. OBJECTIVE: The objective of this study was to translate the CBCL into six languages using a rigorous translation methodology, placing particular emphasis on cultural adaptation and ensuring that the measure has content validity with carers of children with epilepsy. METHODS: A rigorous translation and cultural adaptation methodology was used. This is a process which includes two forward translations, reconciliation, two back-translations, and cognitive debriefing interviews with five carers of children with epilepsy in each country. In addition, a series of open-ended questions were asked of the carers in order to provide evidence of content validity. RESULTS: A number of cultural adaptations were made during the translation process. This included adaptations to the examples of sports and hobbies. An addition of "milk delivery" was made to the job examples in the Malayalam translation. In addition, two sexual problem items were removed from the Hebrew translation for Israel. CONCLUSION: An additional six translations of the CBCL are now available for use in multinational studies. These translations have evidence of content validity for use with parents of children with epilepsy and have been appropriately culturally adapted so that they are acceptable for use in the target countries. The study highlights the importance of a rigorous translation process and the process of cultural adaptation.

Retrospective drug utilization review: impact of pharmacist interventions on physician prescribing.

OBJECTIVES: To evaluate the impact of retrospective drug utilization review (RDUR), pharmacist's interventions on physician prescribing, and the level of spillover effect on future prescriptions following the intervention. METHODS: A retrospective case-control study was conducted at a pharmacy benefits management company using the available prescription data from April 2004 to August 2005. RDUR conflicts evaluated and intervened by a clinical pharmacist served as a case group, whereas conflicts that were not evaluated and intervened by a clinical pharmacist served as a control group. RESULTS: A total of 40,284 conflicts in cases and 13,044 in controls were identified. For cases, 32,780 interventions were considered nonrepetitive, and 529 were repetitive. There were 22,870 physicians in cases that received intervention letters and 2348 physicians in the control group that would have received intervention letters during the study period. Each physician received on average 1.4 interventions for cases vs 3.0 for controls. Among the case physicians who were intervened during the study period, 2.2% (505) were involved in a repeated intervention vs 18.2% (428) in controls (P < 0.001), which is an eight-fold difference. The most common conflict intervened on in cases was therapeutic appropriateness (8277, 25.3%), and for controls it was drug-drug interactions (1796, 25.4%). The overall interventional spillover effect in cases was 98.4% vs 89.4% in controls (P = 0.01). CONCLUSION: RDUR is an effective interventional program which results in decreased numbers of interventions per physician and provides a significant impact on future prescribing habits.

A comprehensive review of the literature on epilepsy in selected countries in emerging markets.

AIMS: To perform a systematic literature review of studies in peer reviewed journals on the epidemiology, economics, and treatment patterns of epilepsy in selected countries in emerging markets. METHODS: A literature search was performed using relevant search terms to identify articles published from 1999 to 2000 on the epidemiology, economics, and treatment patterns of epilepsy. Studies were identified through electronic Embase(®), Cochrane(©), MEDLINE(®), and PubMed(®) databases. Manual review of bibliographies allowed for the detection of additional articles. RESULTS: Our search yielded 65 articles. These articles contained information relevant to epidemiology (n = 16), treatment guidelines (n = 4), treatment patterns (n = 33), unmet needs (n = 4), and economics (n = 8). From a patient perspective, patients with less than or equal to two adverse events (AEs) while taking anti-epileptic drugs (AEDs) had significantly lower annual costs than those having greater than or equal to three AEs, as did patients with fewer seizures. The overall mean annual cost for epilepsy per patient ranged from US$773 in China to US$2646 in Mexico. Prevalence data varied widely and were found for countries including Arab League Members, China, India, and Taiwan. In Turkey, active prevalence rates ranged from 0.08/1000 to 8.5/1000, and in Arab countries, active prevalence ranged from 0.9/1000 in Sudan to 6.5/1000 in Saudi Arabia. Seventeen different AEDs were used in the identified studies. The most common AEDs utilized were phenobarbital (21.7%), valproate (17.5%), and tiagabine (16.4%). In all studies, the use of AEDs resulted in an increase of patients who became seizure free and a reduction in seizure frequency and severity. CONCLUSION: Few studies have examined the prevalence and incidence of epilepsy in emerging markets and study limitations tend to underestimate these rates at all times. More cost-effectiveness, cost-minimization, and cost-benefit analyses must be performed to enhance the data on the economics of epilepsy and its therapy in regions with insufficient resources and those emerging markets which contain the majority of the world's population. And finally, the study found that generic AEDs are frequently used to successfully treat patients with epilepsy in emerging markets.

Causes and consequences of injuries in children in Western Australia.

OBJECTIVE: To identify the common causes and consequences of pediatric injury-related admission to an Australian children's hospital. METHODS: A retrospective study was conducted at a pediatric teaching hospital. Patients < 18 years of age hospitalized between March 1, 2007 and April 30, 2007 were included. Patient medical records were reviewed if an admission diagnosis was injury related. Data collected included date of birth, gender, date of admission, date of discharge, diagnosis, procedure, and causes and outcomes of the injury. RESULTS: A total of 184 patients were admitted as a result of injury during the study period. Of these, one neonate, six infants, 38 toddlers, 111 children, and 28 teenagers were included in this study. The most common cause of injury-related hospital admission was a fall (n = 109, 59%). Other causes of injury included crushing (8%, n = 15), the spilling of fluids (5.4%, n = 10), and bites (4.3%, n = 8). The most common consequence of an injury for children (43/111, 38.7%) and teenagers (12/28, 43%) was bone fracture. However, head injuries were the most common injury in toddlers (11/38, 29%), infants (5/6, 83.3%), and neonates (1/1, 100%). The radius and/or ulna (36/63, 57%) were the most common bones fractured. The majority (32/37, 86.5%) of patients who suffered head injuries were diagnosed as having a minor injury. CONCLUSION: The main cause of injury-related admission to the hospital for children was a fall, with the most common consequences being fractures and head injuries.

Treatment patterns and resource utilization and costs among patients with pulmonary arterial hypertension in the United States.

OBJECTIVE: To explore treatment patterns and resource utilization and cost for subjects with pulmonary arterial hypertension (PAH). RESEARCH DESIGN: Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization. RESULTS: In the final sample of PAH patients treated with bosentan (n=251) or sildenafil (n=455), average age was 57 years, 86% of patients were commercially insured, and 52% of patients were male. Gender distribution varied significantly across subgroups, with a lower proportion of males in the bosentan (30%) subgroup compared with the sildenafil group (64%) (p<0.001). Average baseline Charlson comorbidity score was 2.4. Average numbers of fills per month were 0.8 and 0.4 for bosentan and sildenafil patients, respectively (p<0.001). Over 80% of patients received only one PAH treatment in the first 90 days following the index date, with 28% of bosentan and 13% of sildenafil patients receiving combination therapy (p<0.001). Over one-third of bosentan patients and one-quarter of sildenafil patients experienced a dose increase in the follow-up period (p=0.009). Sixteen percent of sildenafil patients experienced a dose decrease in the follow-up period, while a smaller proportion of patients receiving bosentan (4%) experienced a dose decrease (p<0.001). On average, number of PAH-related per subject per month (PSPM) inpatient stays and emergency department visits and PSPM length of inpatient stays were statistically similar between the subgroups. PAH-related PSPM healthcare costs were high for both subgroups, with average monthly costs of $5,332 and $3,632 among bosentan and sildenafil patients, respectively (p=0.003). Differences in total costs were driven mainly by differences in pharmacy expenditures. CONCLUSIONS: Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, such as the potential for coding errors and lack of information on whether a drug was taken as prescribed. Furthermore, PAH severity (WHO functional class) was not assessed.

Tadalafil therapy and health-related quality of life in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive lung disorder that impairs performance of daily activities and quality of life (QoL), leading to right heart failure and death. Treatment options include prostanoids, endothelin antagonists, and phosphodiesterase type 5 inhibitors (e.g., tadalafil). Currently there is no cure for PAH, but tadalafil has improved exercise capacity in these patients. OBJECTIVES: To explore the effect of tadalafil on health-related quality of life (HRQoL) measures. RESEARCH DESIGN AND METHODS: The Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) clinical trial examined the efficacy and tolerability of tadalafil for the treatment of PAH. The impact of tadalafil on HRQoL and exercise capacity, as measured by 6-minute walk test (6MW test), was also examined. Change from baseline to last non-missing post-baseline was examined for the SF-36, EQ-5D, and 6MW test, along with the relationship between HRQoL and 6MW test performance. RESULTS: Tadalafil 40 mg showed significant improvement over placebo for six of eight SF-36 domains, and EQ-5D index scores. Also, the tadalafil 40-mg group showed significant improvement over placebo on the 6MW test (p < 0.001), but no clear relationship was found between 6MW test performance and HRQoL. CONCLUSION: Results suggest that tadalafil 40 mg may significantly improve HRQoL and exercise capacity for PAH patients. Limitations of this study include its relatively short nature limited to 16 weeks and the relative heterogeneity of the study population.