Fidaxomicin for Clostridium difficile-associated diarrhoea: epidemiological method for estimation of warranted price.

BACKGROUND: Fidaxomicin is a macrocyclic antibiotic approved in 2011 by the US Food and Drug Administration for treatment of Clostridium difficile-associated diarrhoea (CDAD). OBJECTIVE: Herein, we present an epidemiological method to estimate, on a case mix basis, and from the perspective of the US health system, the warranted (justifiable) price per day for fidaxomicin, as a percent of the wholesale acquisition cost (WAC) per day for fidaxomicin ($US280). METHODS: Data from two randomized controlled studies (Optimer-003 [n = 596] and Optimer-004 [n = 509]) were used to discern the number-needed-to-treat (NNT = 7.1) for sustained clinical response. Sustained clinical response was defined as clinical response at the end of treatment, and survival without proven or suspected CDAD recurrence through 25 days beyond the end of treatment. National data for primary and secondary cases (the case mix) of CDAD (mean hospital length of stay [LOS], and mean cost) were derived from the 2009 US Healthcare Cost and Utilization Project. The method for attribution of hospital LOS for secondary cases of CDAD was derived from a study published by O'Brien et al. in 2007. Comparative regimens of vancomycin were: (i) injectable used orally, 125 mg four times daily (qid; WAC of $US6/day), with use of vancomycin hydrochloride (HCl) capsules, 125 mg qid (WAC of $US106/day) post-hospital discharge; (ii) vancomycin HCl capsules, 125 mg qid; and (iii) vancomycin HCl capsules, 250 mg qid (WAC of $US196/day). Findings are expressed in 2011 US dollars. The study perspective is that of the US health system. RESULTS: The warranted price per day for fidaxomicin represented 95% of the WAC per day for fidaxomicin compared with use of injectable vancomycin (orally) 125 mg qid (with subsequent use of vancomycin HCl capsules, 125 mg qid post-hospital discharge); 109% of the WAC per day for fidaxomicin compared with use of vancomycin HCl capsules, 125 mg qid; and 141% of the WAC per day for fidaxomicin when compared with use of vancomycin HCl capsules, 250 mg qid. CONCLUSION: From the perspective of the US health system, fidaxomicin represents value for money in the treatment of CDAD. The methodology employed in this research has application beyond antimicrobial pharmacotherapy.

α1-Proteinase inhibitor (human) in the treatment of hereditary emphysema secondary to α1-antitrypsin deficiency: number and costs of years of life gained.

BACKGROUND: α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typically presents with a serum α-AT level of <50 mg/dL. In severe α-ATD, phenotype PiZZ, protection of the lungs is compromised, leading to an accelerated decline in forced expiratory volume in 1 second (FEV(1)). As a result, a patient may develop pulmonary emphysema of the panacinar type at a young age (third to fourth decades of life), with cigarette smoking being the most significant additional risk factor. It has been shown that weekly or monthly infusion of human α-AT is effective in raising serum α-AT levels to desired levels (>80 mg/dL), with few, if any, adverse effects. OBJECTIVE: The present study was designed to discern the number of years of life gained, and the expense per year of life gained, associated with use of α-AT augmentation therapy (α(1)-proteinase inhibitor [human]), relative to 'no therapeutic intervention' in persons with α-ATD. METHODS: Monte Carlo simulation (MCS) was used to: (i) estimate the number of years of life gained; and (ii) estimate the health service expenditures per year of life gained for persons receiving, or not receiving, α-AT augmentation therapy. MCS afforded a decision-analytical framework parameterized with both stochastic (random) and deterministic (fixed) components, and yielded a fiscal risk-profile for each simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or past use (smoker)]; and use of α-AT augmentation therapy). The stochastic components employed in the present inquiry were: (i) age-specific body weight, and height; (ii) age-specific mortality; and (iii) the probability distribution for receipt of a lung transplant, as a function of FEV(1). The deterministic components employed in the present inquiry were: (i) age in years for the simulated cohort; (ii) outlays for α-AT augmentation therapy; (iii) health service expenditures associated with receipt of a lung transplant; (iv) annual decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of α-AT augmentation therapy as a function of percent predicted FEV(1); (vii) need for a lung transplant as a function of percent predicted FEV(1); (viii) annual rate of lung infection; and (ix) mortality as a function of percent predicted FEV(1). Results are reported from a payer perspective ($US, year of costing 2010). RESULTS: Receipt of α-AT augmentation therapy was associated with a significant increase (p < 0.05) in years of life gained, with female smokers gaining an estimated mean 7.14 years (cost per year: $US248 361 [95% CI 104 531, 392 190]); female non-smokers gained an estimated mean 9.19 years (cost per year: $US160 502 [95% CI 37 056, 283 947)]); male smokers gained an estimated mean 5.93 years (cost per year: $US142 250 [95% CI 48 467, 236 032]); and male non-smokers gained an estimated mean 10.60 years (cost per year: $US59 234 [95% CI 20 719, 97 548]). CONCLUSION: Use of α-AT augmentation therapy was associated with an increase in years of life gained by sex and history of tobacco use, and at a cost per year of life gained comparable to that of other evidenced-based interventions.

Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug Administration alert on serotonin syndrome.

OBJECTIVE: The present study was designed to discern the prevalence of concomitant use of a 5-hydroxytryptamine receptor agonist (triptan), and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) after the US Food and Drug Administration issued an alert regarding serotonin syndrome in 2006 and to contrast findings with data published prior to the federal warning. BACKGROUND: In July 2006, the US Food and Drug Administration warned patients and health-care professionals to be aware that use of a triptan in combination with an SSRI or SNRI may result in a potentially life-threatening problem known as serotonin syndrome. In 2010, the American Headache Society published a position paper noting that there existed conflicting and insufficient information to discern the risk of serotonin syndrome with the use of triptan, and SSRI or SNRI, and that said Class IV data were not to be used as the basis for limiting the prescribing of triptan with SSRI or SNRI (Level U). Clinicians were cautioned as to the seriousness of serotonin toxicity and that monitoring was warranted. METHODS: We used weighted data from the US National Ambulatory Medical Care Survey for years 2007 and 2008 to derive national estimates of the number of office-based physician-patient encounters (visits), documenting the concomitant use of triptan, and SSRI or SNRI. Results are compared with previously published findings for the years 2003 and 2004. RESULTS: During the time-frame 2007-2008, an annualized mean of 5,256,958 patients were prescribed a triptan (vs 3,874,367 in 2003-2004, a 35.7% increase), and 68,603,600 patients were prescribed an SSRI or SNRI (vs 50,402,149 in 2003-2004, a 36.1% increase). An annualized mean of 1,319,763 patients were simultaneously prescribed or continued use of triptan, along with SSRI or SNRI (vs 694,276 in 2003-2004, a 90.1% increase). CONCLUSION: Our study documents that 1.8% (1,319,763/73,860,558) of patients in 2007-2008 were prescribed triptan, and SSRI or SNRI (vs 1.3% in 2003-04, an increase of 38.5%). While this is a small fraction overall, the actual number of patients on a nationwide basis is substantial. What remains missing from the literature is documentation as to the number of cases of serotonin syndrome and resulting consequences (clinical and economic) because of the concomitant use of triptan, and SSRI or SNRI in the time-frame 2007-2008. Absent in these data, it remains difficult to assess the risk benefit associated with the use of triptan, and SSRI or SNRI.

Diagnosis of depression and use of antidepressant pharmacotherapy among adults in the United States: does a disparity persist by ethnicity/race?

BACKGROUND AND OBJECTIVE: Both the rate of diagnosis of depression in the US and the rate of prescribing an antidepressant for its treatment have increased substantially over the past two decades. Previous research has also indicated that the rates of diagnosis and treatment of depression with an antidepressant vary widely by ethnicity/race. The objective of this study was to discern ethnic/race-specific (non-Hispanic Black; Hispanic; non-Hispanic White) population-adjusted rates of US office-based physician-patient encounters (office-based visits) documenting a diagnosis of depression, and the extent of the use of antidepressant pharmacotherapy for its treatment. METHODS: Data from the US National Ambulatory Medical Care Survey (NAMCS) for the years 1992-1997 and 2003-2008 were utilized for this analysis. The years 1998-2002 were excluded due to the magnitude of missing data for the variable ethnicity. The US NAMCS is a national probability sample designed and conducted by the US National Center for Health Statistics of the US Centers for Disease Control and Prevention. Depression was defined via International Classification of Diseases, 9th Revision, Clinical Modification codes 296.2-296.36; 300.4; 311. Antidepressants were defined as US National Drug Code category 0630 prior to 2005, and category 249 in Lexicon Plus® thereafter. Data were partitioned into six 2-year time intervals for trend analysis of population-adjusted rates (per 100) among patients aged 20-79 years. Rates per 2-year time interval are based on US Census Bureau national resident population estimates for the ethnicity/race categories examined. Comparisons within and across time-frames were assessed by chi-squared (χ2) analysis. The a priori level of significance for all statistical tests was set at p < 0.05. Analyses were performed using SAS Release 9.1.3. RESULTS: Over the 12-year time-frame examined, the rate of office-based visits documenting a diagnosis of depression increased 28.4% for non-Hispanic Whites (from 10.9 to 14.0 per 100; p < 0.001), 54.8% for non-Hispanic Blacks (from 4.2 to 6.5 per 100; p < 0.001), and 37.5% for Hispanics (from 4.8 to 6.6 per 100; p < 0.001). The rate of office-based visits with a recorded diagnosis of depression in concert with the prescribing of an antidepressant increased 66.2% for non-Hispanic Whites (from 6.5 to 10.8 per 100; p < 0.001), 69.2% for non-Hispanic Blacks (from 2.6 to 4.4 per 100; p < 0.001), and 36.7% for Hispanics (from 3.0 to 4.1 per 100; p < 0.001). CONCLUSION: By 2003-2004, the population-adjusted rates for non-Hispanic Blacks and Hispanics were similar, and remained so through 2007-2008. However, over the 12-year time-frame examined, the rates for both minority groups were, in each 2-year interval, far less than that observed in non-Hispanic Whites. Disparities remain by ethnicity/race in the diagnosis and treatment of depression in the US.

Hospital admission for schizophrenia and discharge against medical advice in the United States.

OBJECTIVE: Hospital discharge against medical advice may leave a patient at risk for adverse health outcomes and/or readmission, yet little is known regarding its occurrence, especially among patients with mental illness. The objective of this study was to discern the prevalence of, and predictive factors for, being discharged against medical advice among hospitalized patients with a primary diagnosis of schizophrenia. METHOD: The 2004 US Healthcare Cost and Utilization Project Nationwide Inpatient Sample was used to discern demographic predictors, length of stay, and costs for discharge against medical advice relative to discharge with medical approval. Inpatient discharges from US community hospitals for patients of all ages with The International Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes 295.0-295.9 were included. Conditional logistic regression was used to discern factors predictive of discharge against medical advice, and least squares mean analysis was used to examine differences in length of stay and mean cost per day relative to discharge with medical approval. Least squares means were adjusted for age (continuous), sex, race, region, payer, hospital setting, and bed size. RESULTS: Within the study population, 1.6% of patients admitted for schizophrenia were discharged against medical advice (n = 3,382/210,722). Patients discharged against medical advice were significantly more likely to be younger (OR = 0.985, 95% CI, 0.982-0.987) and male (OR = 1.421, 95% CI, 1.321-1.529). Race was not a significant factor. Mean +/- SE length of stay for discharge against medical advice was 5.0 +/- 0.24 days, as compared to 8.7 +/- 0.06 days for patients discharged with medical approval (P < .0001). Mean cost per day was significantly higher for discharge against medical advice ($1,886.02 +/- 49.67 vs $1,565.79 +/- 13.42, P < .0001). CONCLUSIONS: Although the percentage of patients discharged against medical advice was small, the numeric magnitude on a nationwide basis was substantial. The adjusted mean length of stay for discharge against medical advice was significantly reduced, while cost per day was significantly higher. Discharge against medical advice represents a challenge to the provision of care for patients with schizophrenia and may contribute to increased use of primary and specialty outpatient services, rehospitalization rates, morbidity, and mortality.

Ethnicity/race, use of pharmacotherapy, scope of physician-ordered cholesterol screening, and provision of diet/nutrition or exercise counseling during US office-based visits by patients with hyperlipidemia.

BACKGROUND: Elevation of serum cholesterol, or hyperlipidemia, is recognized as one of the major modifiable risk factors in the development of atherosclerosis and cardiovascular disease. On a US population basis, there has been a downward trend in total- and LDL-cholesterol levels, and an increase in cholesterol screening. Nevertheless, previous research suggests that there remain racial/ethnic disparities in the access to and quality of care for hyperlipidemia. OBJECTIVE: The aim of this study was to examine the extent of racial/ethnic disparities in the provision of pharmacotherapy, cholesterol screening and diet/nutrition or exercise counseling during US office-based physician-patient encounters (visits) by patients with hyperlipidemia. METHODS: We examined data from the 2005 US National Ambulatory Medical Care Survey for office-based visits for hyperlipidemia for patients aged > or =20 years in terms of prescribing for hyperlipidemia, and the ordering/provision of cholesterol testing, diet/nutrition counseling, and exercise counseling. RESULTS: Use of pharmacotherapy for hyperlipidemia varied by ethnicity/race (chi2, p < 0.05). Physician-ordered/provided cholesterol screening occurred in 44.2% of all office-based visits; 46.5% for Whites, 35.4% for Blacks, and 30.3% for Hispanics (chi2, p < 0.05). Diet/nutrition counseling was ordered/provided in 39.7% of office-based visits; 40.4% for Whites, 32.6% for Blacks, and 39.0% for Hispanics (chi2, p < 0.05). Exercise counseling was ordered/provided in 32.1% of office-based visits; 32.7% for Whites, 27.2% for Blacks, and 30.6% for Hispanics (chi2, p < 0.05). CONCLUSIONS: These findings reveal a disparity in use of pharmacotherapy for hyperlipidemia, physician-ordered/provided cholesterol screening, diet/nutrition counseling, and exercise counseling by ethnicity/race. Further research is required to discern, in greater detail, reasons for the observed differences reported, and to ensure equitable access to established standards of care.

Trends in prescriptions for antidepressant pharmacotherapy among US children and adolescents diagnosed with depression, 1990 through 2001: an assessment of accordance with treatment recommendations from the American Academy of Child and Adolescent Psychiatry.

BACKGROUND: In 1998, the American Academy of Child and Adolescent Psychiatry (AACAP) published a position paper supporting the use of selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacotherapy for the treatment of depression among children and adolescents. Tricyclic antidepressants (TCAs) were not recommended because of insufficient efficacy evidence, as well as adverse events. OBJECTIVE: The present study was designed to discern the prescribing patterns for antidepressants among US children and adolescents aged 5 to 18 years diagnosed with depression between 1990 and 2001 (ie, before and after the publication of the AACAP paper). METHODS: Data derived from the US National Ambulatory Medical Care Survey for the years 1990 through 2001 were used for this retrospective, cross-sectional analysis examining children and adolescents aged 5 to 18 years. Information from physician-patient encounters (office-based visits), documenting a diagnosis of depression (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 296.2-296.36, 300.4, or 311) were extracted. Data were categorized into three 4-year time intervals: 1990 through 1993; 1994 through 1997; and 1998 through 2001. RESULTS: Overall, the rate of antidepressant prescriptions for US patients who received a diagnosis of depression increased from 44.4% (1,138,689/2,561,890) in the period from 1990 through 1993 to 59.3% (4,103,683/6,923,040) in the period from 1998 through 2001. SSRI prescriptions increased from 20.7% (530,642/2,561,890) in the period from 1990 through 1993 to 39.7% (2,745,293/6,923,040) in the period from 1998 through 2001; TCA prescriptions decreased from 21.0% (537,906/2,561,890) in the period from 1990 through 1993 to 2.7% (188,823/6,923,040) in the period from 1998 through 2001. The US population-adjusted rate of a diagnosis of depression with or without comorbid mental illness (ICD-9-CM codes 290-296.19, 296.4-300.39, 300.5-310.99, or 312.0-319) increased 2.4-fold from 12.9 per 1000 in the period from 1990 through 1993 to 31.1 in the period from 1998 through 2001. Among these patients, the prescribing of an antidepressant increased 3.2-fold (5.7 per 1000 in the period from 1990 through 1993 to 18.4 in the period from 1998 through 2001). The population-adjusted rate of SSRI prescribing increased 4.6-fold from 2.7 per 1000 children and adolescents in the period from 1990 through 1993 to 12.3 in the period from 1998 through 2001. CONCLUSIONS: From 1990 through 2001, prescription patterns for antidepressant pharmacotherapy among children and adolescents aged 5 to 18 years changed. In accordance with the recommendation made by the AACAP in 1998, prescriptions for SSRIs increased, whereas prescriptions for TCAs all but disappeared.

Rate of obesity in U.S. ambulatory patients with diabetes mellitus: a national assessment of office-based physician visits.

To examine the interface between obesity and type 2 diabetes mellitus we examined data from the 2005 U.S. National Ambulatory Medical Care Survey (NAMCS). Our findings indicate a significant proportion of U.S. ambulatory patients with DM present with obesity and greater clinical acuity than patients with DM alone.

Prevalence of depression and use of antidepressant pharmacotherapy among ambulatory patients with diabetes mellitus in the United States.

BACKGROUND: Persons with diabetes mellitus (DM) exhibit a higher rate of depressive illness than does the general US population. Despite this finding, previous research has documented a low rate of diagnosis and/or treatment with antidepressant pharmacotherapy among persons with DM. OBJECTIVE: The aim of this study was to examine the current rate of diagnosis of depression and use of antidepressant pharmacotherapy among persons with DM. RESULTS: We examined data from the 2005 US National Ambulatory Medical Care Survey. In 2005, there were an estimated 35,345,845 persons with an office-based visit for DM and, of these, 3,823,508 (10.8%) had a concomitant diagnosis of depression. Within this subset, 1,830,620 (47.9%) were prescribed antidepressant pharmacotherapy. CONCLUSION: Our findings serve to quantify the prevalence of a diagnosis of depression and use of antidepressant pharmacotherapy for its treatment among persons with DM in the United States.

Ethnicity/race and the diagnosis of depression and use of antidepressants by adults in the United States.

The objective of this study is to discern ethnic/race-specific (black, Hispanic, white) population-adjusted rates of US office-based visits documenting a diagnosis of depression, and the extent of the use of antidepressant pharmacotherapy for its treatment. Data from the National Ambulatory Medical Care Survey for the time-frames 1992-1997, and 2003-2004, were partitioned into four, 2-year time intervals for trend analysis among patients aged 20-79 years. From 1992-1993 to 2003-2004, the annualized rate of visits documenting a diagnosis of depression increased from 10.9 to 15.4 per 100 US population for whites, from 4.2 to 7.6 for blacks, and from 4.8 to 7.0 for Hispanics. A concomitant diagnosis of depression and antidepressant use increased from 6.5 to 11.4 per 100 for whites, from 2.6 to 5.2 for blacks, and from 3.0 to 5.6 for Hispanics. It can be concluded that by 2003-2004, diagnostic and treatment rates were comparable among blacks and Hispanic, but were less than half the observed rates for whites.

Hospital length of stay for children and adolescents diagnosed with depression: is primary payer an influencing factor?

OBJECTIVE: This study aimed (a) to discern the distribution by primary payer (public vs. private) of U.S. patients aged 5-18 years who were hospitalized with a primary diagnosis of depression and (b) to discern the mean hospital length of stay and mean charge per day by payer type. METHODS: The 2003 Healthcare Cost and Utilization Project Kids' Inpatient Database was used for this analysis. Depression was defined as International Classification of Diseases, 9th Revision, Clinical Modification codes 296.2-296.36, 300.4 or 311. Differences in hospital length of stay and mean cost per day by payer type were discerned via adjusted least square mean analysis (+/-S.E.). RESULTS: The adjusted mean hospital length of stay was significantly higher (P<.0001) for patients with a public payer (6.6+/-0.05 days) versus a private payer (5.3+/-0.05 days). Although statistically significant (P<.0001), the adjusted mean charge per day differed little by payer type (public, US$1316.39+/-9.82; private, US$1357.51+/-9.07). CONCLUSIONS: Further research is required to discern whether observed differences in hospital length of stay are the result of private payers enhancing patient care, thereby discharging patients in a more efficient manner, or the patients being discharged prematurely from the hospital due to constraints in reimbursement by private payers.

Concomitant triptan and SSRI or SNRI use: a risk for serotonin syndrome.

OBJECTIVE: To discern the prevalence of concomitant use of a triptan and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) in the USA. BACKGROUND: In July, 2006, the US Food and Drug Administration warned patients and health-care professionals to be aware that use of a triptan in combination with an SSRI or an SNRI may result in a potentially life-threatening problem known as serotonin syndrome. METHODS: We used weighted data from the US National Ambulatory Medical Care Survey for years 2003 and 2004 to derive national estimates of the number of office-based visits documenting concomitant use of a triptan and an SSRI or an SNRI. RESULTS: During the time frame 2003-04, an annualized mean of 3,874,367 patients were prescribed a triptan, and 50,402,149 patients were prescribed an SSRI or an SNRI. An annualized mean of 694,276 patients were simultaneously prescribed or continued use of a triptan along with an SSRI or SNRI. CONCLUSION: Our study documents that 1.3% of patients prescribed a triptan or an SSRI or an SNRI were prescribed the potentially fatal combination. While this is a small fraction overall, the actual number of patients on a nationwide basis is significant (n=694,276).

Trends in the prescribing of oral agents for the management of type 2 diabetes mellitus in the United States, 1990-2001: does type of insurance influence access to innovation?

PURPOSE: The objectives of the present study were (1) to discern trends in the prescribing of oral pharmacotherapy for the management of type 2 diabetes mellitus (DM) in the United States during the years 1990 through 2001 and (2) to examine the mediating role of primary health insurance coverage on patients' access to pharmaceutical innovation for the management of type 2 DM. METHODS: Data from the US National Ambulatory Medical Care Survey (NAMCS) for the years 1990 through 2001 were used for this analysis. RESULTS: National estimates of the number of office-based visits documenting a diagnosis of type 2 DM and the prescribing of an oral medication for glycemic control increased from 7 871 283 in 1990 to 13 730 886 in 2001 (a 74.4% increase). A significantly higher proportion of patients covered by private health insurance were prescribed a newer agent, either alone or as part of a combination regimen of oral agents, as compared to patients covered by either Medicare or Medicaid (chi(2) < or = .001). CONCLUSIONS: Over the time frame of 1995 through 2001, access to pharmaceutical innovation for the management of type 2 DM was mediated by the patient's primary source of health insurance coverage. Future research will need to discern the effect of observed differences in the prescribing of oral agents for the management of type 2 DM on both clinical and economic outcomes and, in light of ongoing discussion regarding health care reform in the United States, to foster clinically rational and equitable access to pharmaceutical innovation.

Economic and epidemiological modelling of full-length antihaemophilic factor (recombinant), plasma/albumin-free method, in previously treated patients with haemophilia A : comparison with B-domain deleted rFVIII, and value of potential viral transmission reduction due to plasma/albumin-free status.

OBJECTIVES: To the extent that current recombinant clotting factor concentrates contain even trace amounts of human or animal protein, there is continuing potential for transmission of nonenveloped viruses, including hepatitis A, and parvovirus, and the theoretical potential for transmission of relatively unknown agents, such as prions (Creutzfeldt-Jakob disease, or its variant). Full-length antihaemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM; Advate), represents a novel pharmacotherapeutic option for the management of haemophilia A. This investigation was designed to discern: (i) the efficacy-based use pattern (International Units [IUs]) of rAHF-PFM versus B-domain deleted rFVIII (BDDrFVIII; ReFacto) required to resolve a bleeding episode (event) among previously treated patients with haemophilia A employing on-demand treatment; (ii) the health service expenditure pattern (percentage differential; payor's perspective) associated with use of rAHF-PFM versus BDDrFVIII among previously treated patients with haemophilia A employing on-demand treatment; and (iii) the fiscal utility attributable to the plasma/albumin-free status of rAHF-PFM under the assumed emergence of a novel and infectious blood (plasma)-borne virus. MATERIALS AND METHODS: Data stemming from phase II/phase III clinical trials of rAHF-PFM, together with published literature on BDDrFVIII, afforded calculation of the probability of occurrence for specific endpoints of interest (e.g. non-response to first infusion). Monte Carlo simulation, a decision-analytical framework parameterised with stochastic (random) and deterministic (fixed) components (10 000 iterations per month [or year] of age examined [3, 6, 9 months; years 1 through 19; and years 20, 30, 40, 50, 60, 70 and 80]) was used to compare: (i) the efficacy-based use pattern by treatment option; and (ii) the health service utilisation-based expenditure pattern by treatment option, accounting for the need for subsequent infusion(s), and potential complications (use of services) stemming from failure of the initial infusion (five scenarios). Theoretical and direct modelling methods for assessing the fiscal utility attributable to the plasma/albumin-free status of rAHF-PFM under the assumed emergence of a novel and infectious blood (plasma)-borne virus were developed. Assumptions included: (i) a low population infection rate (<5%); (ii) annual health service expenditures equivalent to 5% of that observed with HIV/AIDS; and (iii) the number of bleeding events experienced per year were 6, 9 or 12. RESULTS: Monte Carlo simulation-replicated simulations per year of age examined revealed: (i) use of rAHF-PFM resulted in a 12.20% median reduction in the number of IUs required to resolve a bleeding episode (event) relative to BDDrFVIII (p < 0.05); and (ii) a health service utilisation-based savings [primary care; hospital] (p < 0.05; range 13.74-39.34% [dependent on intensity (sequencing) of care required]) with rAHF-PFM relative to BDDrFVIII. The overall scenario-weighted health service utilisation-based savings was 16.94% (p < 0.05). Under the assumption of the emergence of a novel and infectious blood (plasma)-borne virus, deterministic models for persons weighing 20 kg, 50 kg and 80 kg all revealed a savings potential ($US per IU) with use of rAHF-PFM relative to use of a non-plasma/albumin-free product. CONCLUSION: Use of rAHF-PFM in on-demand management of haemophilia A offers enhanced patient safety and represents a fiscally prudent therapeutic strategy.

Treatment modalities among US children diagnosed with attention-deficit hyperactivity disorder: 1995-99.

The objective of this study was to determine the prevalence of single and combination treatment modalities among US children aged 5-18 years who were diagnosed with attention-deficit hyperactivity disorder (ADHD). Treatments included: (i) stimulant pharmacotherapy alone; (ii) psychotherapy and/or mental health counselling alone; (ii) a combination; or (iv) no treatment. Data from the US National Ambulatory Medical Care Survey (NAMCS) for the years 1995-99, were used for this analysis. Office-based physician-patient visits documenting a recorded diagnosis of ADHD (ICD-9-CM codes 314.00 or 314.01) were extracted from the NAMCS. Findings are presented for children diagnosed with ADHD with or without comorbid mental illness, for children diagnosed with ADHD without comorbid mental illness, by gender, and by age groups. Over the timeframe 1995-99, an estimated 14 402 090 office-based visits documented a diagnosis of ADHD, with (24%) or without (76%) comorbid mental illness, among children aged 5-18 years. Overall, the most frequent treatment was stimulant medication alone (42.0%). This was followed by the combination treatment of stimulant medication plus psychotherapy and/or mental health counselling (32.1%). Only 10.8% of the children received psychotherapy and/or mental health counselling alone; 15.1% received no treatment beyond the office-based visit. This pattern was consistent for boys and girls; however, a larger proportion of boys (11.7%) were receiving psychotherapy and/or mental health counselling alone than girls (8.2%). More girls (18.7%) were receiving no treatment option compared to boys (13.9%). The percentage of children receiving psychotherapy and/or mental health counselling alone increased with each age group (6.7%, 5-8 years; 11.3%, 9-12 years; 13.6%, 13-18 years), as did the combination treatment of stimulant medication plus psychotherapy and/or mental health counselling (28.2%, 31%, 37.3%, respectively). Only 8.2% of children age 13-18 years were receiving no treatment option compared to 16.9% of children age 9-12 years, and 19.5% of those aged 5-8 years. The reasons for the gender and age group differences discerned in this study require further investigation, as does the reason why 15.1% of children were receiving no treatment beyond the office-based visit.

Is attention deficit hyperactivity disorder increasing among girls in the US? Trends in diagnosis and the prescribing of stimulants.

OBJECTIVE: To use a single national data source to discern trends in the prevalence of office-based visits resulting in a diagnosis of attention deficit hyperactivity disorder (ADHD) among girls, and trends in the prescribing of stimulant pharmacotherapy (including methylphenidate) for its treatment in the US. METHODS: Data from the US National Ambulatory Medical Care Survey were utilised for this analysis. The number and rate of office-based physician visits resulting in a diagnosis of ADHD (International Classification of Diseases, 9th Revision, Clinical Modification code 314.00 or 314.01) were discerned from the beginning of 1990 to the end of 1998, for children aged 5 to 18 years. Gender-specific trend analyses were conducted using four time intervals: 1991 to 1992, 1993 to 1994, 1995 to 1996, and 1997 to 1998. RESULTS: The estimated number of office-based visits documenting a diagnosis of ADHD among children increased from 947 208 in 1990 to 3 234 180 in 1998. The rate of office-based visits documenting a diagnosis of ADHD among children increased from 19.4 per 1000 of the US population aged 5 to 18 years in 1990 to 59.0 per 1000 in 1998, a 3-fold increase (p < 0.05). The annualised mean number of office-based visits documenting a diagnosis of ADHD among girls tripled between 1991 to 1992 and 1997 to 1998 (from 296 389 to 886 798), whereas the number for boys increased 2.2-fold (from 1 006 243 to 2 200 021). The US population-adjusted rate of office-based visits documenting a diagnosis of ADHD among girls increased 2.7-fold between 1991 to 1992 and 1997 to 1998 (from 12.3 per 1000 girls to 33.4 per 1000; p < 0.05), whereas the rate among boys doubled (from 39.5 per 1000 boys to 78.7 per 1000; p < 0.05). Documentation of a diagnosis of ADHD and the prescribing of stimulant pharmacotherapy increased 2.8-fold for girls, from 7.5 per 1000 girls in 1991 to 1992 to 21.1 per 1000 in 1997 to 1998 (p < 0.05), as compared with a 2.2-fold increase among boys (from 25.5 per 1000 boys to 57.0 per 1000; p < 0.05). CONCLUSION: Over the time frame 1990 to 1998, the rate of ADHD as well as the prescribing of stimulant medications for its treatment increased significantly among children aged 5 to 18 years. Between 1991 to 1992 and 1997 to 1998, the increased rate of diagnosis of ADHD among girls contributed to the overall upward trend. The rapidly increasing rate of ADHD among girls, and the prolonged nature of the disorder, represent significant public health problems. There exists a need for additional research examining both the aetiology and treatment of ADHD by gender.