Methenamine for urinary tract infection prophylaxis: A systematic review.

Urinary tract infections (UTIs) commonly affect many patient populations. Recurrent UTIs (rUTIs) can be particularly problematic and lead to potential hospitalizations, multiple antibiotic courses, and have a potential negative impact on quality of life. To prevent UTIs, antibiotics are frequently used for prophylaxis; however, antibiotic prophylaxis has notable untoward consequences including but not limited to potential adverse effects and development of antibiotic resistance. Methenamine, an antiseptic agent initially available in 1967, has re-emerged as a potential option for UTI prophylaxis in various populations, including older adults and renal transplant recipients. The objective of this systematic review was to evaluate the clinical effectiveness and safety of methenamine for UTI prophylaxis. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance was performed. A PubMed, Embase, and Cochrane library search was conducted to identify relevant English-language studies evaluating methenamine for UTI prophylaxis including randomized controlled trials, case-control studies, and meta-analyses through June 2023. Articles were excluded if the studies did not primarily describe or evaluate methenamine for UTI prophylaxis, were commentaries/viewpoints articles, point prevalence studies, review articles, studies that evaluated methenamine used with another agent, and any duplicate publications from searched databases. A total of 11 articles were identified for inclusion. This systematic review suggests methenamine generally appears to be an effective and well-tolerated antibiotic-sparing option for UTI prophylaxis. Furthermore, the pharmacology, dosage and formulation, warnings, precautions, and safety considerations of methenamine that provide potential clinical considerations regarding its use for UTI prophylaxis are described. Further studies are needed to evaluate the clinical utility of methenamine for UTI prophylaxis.

Pharmacist prescribed hormonal contraceptives in New York State: Is there a need and an interest?

BACKGROUND: Hormonal contraceptives are a popular option for pregnancy prevention and other indications and require a prescription. Since 2013, 24 states have given pharmacists legal authority to initiate self-administered hormonal contraceptives, allowing for direct pharmacy access (DPA). New York State (NYS) did not allow for DPA of any hormonal contraceptives during the survey period, but passed a bill in 2023 allowing pharmacists to dispense hormonal contraceptives in accordance with a nonpatient-specific order. OBJECTIVES: This study aimed to characterize the experiences, perceptions, and knowledge of access to and DPA to hormonal contraceptives. METHODS: A survey was developed to gather responses to demographic- and opinion-related questions and administered online using the Pollfish survey platform. Participants were women between the ages of 16 and 44 years who lived in NYS. To ensure geographic representation, at least one response was gathered from each of the 27 NYS congressional districts. Chi-square tests were used to assess differences in hormonal contraceptive use by patient demographics. RESULTS: Most of the 500 respondents reported past (76.2%) or current/planned (76.8%) use of hormonal contraceptives. Older age (P = 0.033) and higher income (P = 0.0016) were associated with significantly greater rates of use. The most common challenges when visiting a provider for birth control included needing to schedule an appointment and wait times at the provider. Almost three-quarters of respondents (72.6%) were not aware that pharmacists could initiate contraceptives in other states, and 74.2% reported feeling comfortable with a pharmacist prescribing and dispensing hormonal contraceptives. CONCLUSION: Contraceptive initiation by pharmacists would be acceptable to most respondents, but there is room for increased acceptance based on patient education and experience. DPA to hormonal contraceptives may eliminate some of the barriers identified in this survey.

Evaluation of temperature excursions from USP <659> recommendations during mail transit.

BACKGROUND: Patients use mail delivery as a convenient alternative to acquiring medications in person. Federal laws require nonspecialty oral medications to be stored at controlled room temperature during distribution; however, no laws or regulations govern temperature requirements for medication transport among patients, which may expose medications to harmful temperature excursions. OBJECTIVE: The purpose of this study was to evaluate temperature excursions during mail transit based on the shipment method, carrier, and season. METHODS: This prospective study monitored temperature fluctuations during simulated mail transit between New Jersey, California, and Tennessee over winter (December 2019-February 2020) and summer (August-September 2020) time frames. Packages with data-logging thermometers were shipped to 3 U.S. destinations via 3 common mail carriers and 2 popular shipping methods. Three packages were mailed for each combination of season, carrier, and shipping method, representing 36 individual packages. The primary end point was percent of transit time out of range (OOR) based on the United States Pharmacopeia <659> recommended range, 68°F to 77°F. Additional end points include package transit durations and extreme temperatures. RESULTS: Evaluated packages spent an average of 68.3% of transit time OOR. In winter, 3-day and next business day packages spent similar time OOR (80.1% vs. 78%). In summer, 3-day packages spent more time OOR compared with next business day shipping (43.1% vs. 13.6%). Mean transit time was statistically significantly longer for 3-day packages (406.6 hours vs. 303.1 hours; P < 0.0001). Mean winter transit time was statistically significantly longer than summer (475.7 hours vs. 233.9 hours; P < 0.001) regardless of the shipping method. The minimum and maximum temperatures recorded were 5.1°F and 102.3°F, respectively. CONCLUSION: Package temperatures were outside of the recommended range for most of the transit time regardless of the shipping method, carrier, or season.

Global Health Impact: A Model to Alleviate the Burden and Expand Access to Treatment of Neglected Tropical Diseases.

Neglected tropical diseases (NTDs) receive relatively little research and development but have a tremendous impact on lifespan and livelihood. Here, we use existing data on the need for drugs, their efficacy, and their treatment percentages to estimate the impacts of various regimens on the global burden of several NTDs: schistosomiasis, onchocerciasis, lymphatic filariasis, and three soil-transmitted helminths (STHs) over time. For an interactive visualization of our models' results, see https://www.global-health-impact.org/. In 2015, our NTD models estimate that treatment averted 2,778,131.78 disability-adjusted life years (DALYs). Together, treatments targeting STHs together averted 51.05% of the DALYs averted from all NTD treatments, whereas schistosomiasis, lymphatic filariasis, and onchocerciasis medicines averted 40.21%, 7.56%, and 1.18%, respectively. Our models highlight the importance of focusing not just on the burden of these diseases but also on their alleviation in the effort to expand access to treatment.

Opioid abuse risk among student pharmacists.

OBJECTIVE: To benchmark opioid abuse risk among student pharmacists attending three northeast pharmacy schools utilizing the opioid risk tool (ORT). DESIGN: A cross-sectional, anonymous risk assessment questionnaire. SETTING: Three pharmacy schools in the northeast United States. PARTICIPANTS: Professional year 1 (P1) through professional year 3 (P3) student pharmacists. METHODS: ORT was collected and scored by investigators and inputted into an electronic format for analysis. Students voluntarily participated, and 812 surveys were completed during one course meeting time and day at each school. RESULTS: The majority of students were in the low-risk category (n = 581, 71.6 percent). Additionally, 137 (16.9 percent) patients were categorized as moderate risk and 94 (11.6 percent) as high risk. No statistically significant differences existed when comparing risk groups across the first through third professional year student pharmacist cohorts. There were no statistically significant differences in the proportion of risk groups among the three pharmacy cohorts between low-risk versus the high-risk groups. When comparing risk groups by gender, males were found to have a statistically significant higher proportion of being classified as moderate or high risk. CONCLUSIONS: The results of this study demonstrate that there may be some student pharmacists with an increased risk for opioid abuse potential. There is potential need for education regarding opioid risk awareness and abuse prevention, which may serve as a call to action for professional school students and practitioners to understand baseline opioid abuse risk if they require chronic pain therapy.

A framework for assessing the impact of disease treatment.

OBJECTIVES: To address ongoing pandemics and epidemics, policy makers need good data not only on the need for treatments but also on new interventions' impacts. We present a mathematical model of medicines' health consequences using disease surveillance data to inform health policy and scientific research that can be extended to address the current public health crisis. METHODS: The Global Health Impact index calculates the amount of mortality and morbidity averted by key medicines for malaria, TB, HIV/AIDS and several Neglected Tropical Diseases (NTDs) using data on outcomes in the absence of treatment, treatment effectiveness and access to needed treatment. Country-level data were extracted from data repositories maintained by the Global Burden of Disease study, Global Health Observatory, WHO, UNICEF and a review of the scientific literature. RESULTS: The index aggregates drug impact by country, disease, company and treatment regimen to identify the spatial and temporal patterns of treatment impact and can be extended across multiple diseases. Approximately 62 million life-years were saved by key drugs that target malaria, TB, HIV/AIDS and NTDs in our latest model year. Malaria and TB medicines together were responsible for alleviating 95% of this burden, while HIV/AIDS and NTD medicines contribute 4% and 1%, respectively. However, the burden of disease in the absence of treatment was nearly evenly distributed among malaria, TB and HIV/AIDS. CONCLUSIONS: A common framework that standardises health impact across diseases and their interventions can aid in identifying current shortcomings on a global scale.

A system dynamics model of infection risk, expectations, and perceptions on antibiotic prescribing in the United States.

RATIONALE, AIMS, AND OBJECTIVES: Inappropriate antibiotic prescribing is still a major concern that can lead to devastating outcomes including antibiotic resistance. This study aimed to simulate the antibiotic prescribing behaviour by providers for acute respiratory tract infections (ARTIs) and to evaluate the impact of patient expectation, provider's perception of patient's expectation to receive a prescription, and patient's risk for bacterial infection, on the decision to prescribe. METHODS: We developed a unique system dynamics (SD) simulation model based on the significant factors that impact the interaction between provider and patient during visits for ARTIs and the decision to prescribe antibiotics. In order to validate the model for different age groups and regions in the United States, we used the sample of 53 000 ARTI patient visits made at outpatient settings between 1993 and 2015, based on the National Ambulatory Medical Care Survey (NAMCS). RESULTS: Simulation results reveal that physician diagnosis for prescribing antibiotics is based on physician's experience from their prior prescribing behaviour, their perception of patient's infection risk, and patient's expectation to receive antibiotics. Also, there are some variations depending on patient's age and residential region. The simulation analysis also depicts the decreasing trend in patient's expectation over the past two decades for most age groups and regions. CONCLUSIONS: Given the high number of unnecessary prescriptions for ARTI, we found that policies are needed to influence provider's prescribing behaviour through patient's expectation and provider's perception regarding those expectations. Our simulation framework can further be used by policymakers to design and evaluate interventions that may modify the interaction between health providers and patients to optimize antibiotic prescriptions among ARTI patients for different regions and age groups.

Opioid prescribing and misuse among dental patients in the US: a literature-based review.

OBJECTIVES: Although health care practitioners have become more cognizant of the hazards of opioid use, opioid misuse has emerged as a leading public health problem in the United States, accounting for 20% of all deaths among older adolescents and young adults. Opioid analgesics are an important component of dental pain management following dental procedures. The aim of this study was to assess the status of literature on dental opioid prescriptions, their misuse, and relevant prevention strategies in the US. DATA SOURCES: A keyword search of MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL (EBSCO), and Web of Science was conducted in July 2018. The search criteria were carefully selected to include all practitioners treating patients presenting with dental issues and was not restricted to dentists. All peer-reviewed publications in the US written in English about patients with dental problems were included. RESULTS: The initial search led to 267 publications; after removing duplicates, the set consolidated to 196. After an appraisal of the title and abstract for relatedness, 82 publications were selected. Three major themes were identified: epidemiology of dental opioid prescriptions; recognition of the dental providers' contribution to opioid prescription practice; pain management protocols and guidelines in dentistry. CONCLUSIONS: There is moderate recognition of the contribution of dental prescriptions to the opioid epidemic. Several tools are available to increase patient education and practitioner knowledge about the safe use of opioids with a focus on patients at greatest risk.

Patient expectation trends on receiving antibiotic prescriptions for respiratory tract infections: A systematic review and meta-regression analysis.

BACKGROUND: Despite a variety of programs developed to control inappropriate antibiotic prescribing for viral infections, antibiotics are still prescribed excessively for Respiratory Tract Infections (RTI). The patient's expectation to receive an antibiotic often influences the clinician's decision and can lead to inappropriate antibiotic prescriptions. Our objective was to investigate the changes in patient expectations over time when presenting with symptoms of a respiratory infection. METHODS: We performed a systematic review of patient's expectation to receive antibiotics for RTIs. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Our search initially identified 12 070 studies, of which 321 studies were eligible for full text review and 37 articles were selected for final evaluation. Meta-regression analysis was used to evaluate the association between patient expectations and different years. Heterogeneity was evaluated using the Q statistic. RESULTS: Patient expectations (effect size) were pooled using a random effects model. The effect-equality test showed heterogeneity among studies (Q = 3304.23, df = 40, P < 0.0001, k = 40, τ2  = 0.63). Meta-regression results revealed that there is a significant linear negative relationship (B = -1.8374, P < 0.05) between patient expectation and year of data collection, at the global level. A similar finding is observed for the subset of studies conducted outside United States (U.S.) (B = -1.2411, P < 0.1). However, there is no discernible trend for patient expectation in the U.S. or among children and adult subgroups. Also, no significant differences are observed between the patient expectations when considering different age groups. CONCLUSION: The trend of patient expectation for receiving antibiotics for RTIs is declining over time on a global level and also outside the U.S.

Vancomycin exposure in patients with methicillin-resistant Staphylococcus aureus bloodstream infections: how much is enough?

BACKGROUND: Contemporary vancomycin dosing schemes are designed to achieve an area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio of ≥400. However, scant clinical data exist to support this target and available data relied on pharmacokinetic formulas based on daily vancomycin dose and estimated renal function (demographic pharmacokinetic model) to estimate AUCs. METHODS: A cohort study of hospitalized, adult, nondialysis patients with methicillin-resistant Staphylococcus aureus bloodstream infections treated with vancomycin was performed to quantitatively evaluate the relationship between vancomycin exposure and outcomes. Bayesian techniques were used to estimate vancomycin exposure profile for day 1 and 2 of therapy for each patient based on their dosing schedule and collected concentrations. Classification and Regression Tree (CART) analysis was used to identify day 1 and 2 exposure thresholds associated with an increased risk of failure. Failure was defined as 30-day mortality, bacteremia was ≥7 days, or recurrence. RESULTS: During the study period, 123 cases met criteria. Failure was uniformly less pronounced (approximately 20% less in absolute value) in patients who achieved the CART-derived day 1 and 2 thresholds for AUC/MIC by broth microdilution and AUC/MIC by Etest. In the multivariate analyses, all risk ratios were approximately 0.5 for all CART-derived AUC/MIC exposure thresholds, indicating that achievement of CART-derived AUC/MIC exposure thresholds was associated with a 2-fold decrease in failure. CONCLUSIONS: These findings establish the critical importance of daily AUC/MIC ratios during the first 2 days of therapy. As with all observational studies, these findings should be interpreted cautiously and validated in a multicenter randomized trial before adoption into practice.

Relationship between time to clinical response and outcomes among Pneumonia Outcomes Research Team (PORT) risk class III and IV hospitalized patients with community-acquired pneumonia who received ceftriaxone and azithromycin.

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indicator of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.

Evaluating the Potential Impact of Pharmacist Counseling on Medication Adherence Using a Simulation Activity.

OBJECTIVE: To evaluate the impact of counseling in a simulated medication adherence activity. DESIGN: Students were randomized into 2 groups: patient medication monograph only (PMMO) and patient medication monograph with counseling (PMMC). Both groups received a fictitious medication and monograph. Additionally, the PMMC group received brief counseling. A multiple-choice, paper-based survey instrument was used to evaluate simulated food-drug interactions, adherence, and perceptions regarding the activity's value and impact on understanding adherence challenges. ASSESSMENT: Ninety-two students participated (PMMC, n=45; and PMMO, n=47). Overall, a significantly higher incidence of simulated food-drug interactions occurred in the PMMO group (30%) vs the PMMC group (22%) (p=0.02). Doses taken without simulated food-drug interactions were comparable: 46.2% (PMCC) vs 41.9% (PMMO) (p=0.19). The average number of missed doses were 3.2 (PMMC) vs 2.8 (PMMO) (p=0.55). Approximately 70% of the students found the activity to be valuable and 89% believed it helped them better understand adherence challenges. CONCLUSION: This activity demonstrated the challenges and important role of counseling in medication adherence.

Pegfilgrastim: a review of the pharmacoeconomics for chemotherapy-induced neutropenia.

For oncology patients, febrile neutropenia (FN) can be a serious and costly toxicity of chemotherapy, often forcing a reduction in chemotherapy dose intensity and/or duration. Several therapeutic agents are used to reduce the occurrence of neutropenic episodes: granulocyte colony-stimulating factors (G-CSFs) and granulocyte-macrophage colony-stimulating factors. Appropriate administration of colony-stimulating factors reduces the risk of FN episodes and the costs associated with FN treatment. In the USA, the two most commonly used G-CSFs are filgrastim and the longer-acting pegfilgrastim. This pharmacoeconomic review of pegfilgrastim briefly considers some of the early research of G-CSFs, then focuses on the most recent comparative studies of pegfilgrastim against the backdrop of forthcoming US patent expiration for both products. The authors conclude with commentary on the market for pegfilgrastim in light of the growing debate surrounding the optimal selection of patients, treatment costs and future alternatives for the use of these agents in chemotherapy.

Variation in the cost of medications for the treatment of colorectal cancer.

OBJECTIVE: To evaluate the economic burden of colorectal cancer (CRC) treatment on the healthcare system as treatment costs have risen 340-fold during the past 5 years. STUDY DESIGN: Nationwide registry. METHODS: Patients with CRC (N = 421) were selected from an observational prospective patient registry of US oncology clinics. The 8 most commonly prescribed regimens were identified. Standard dosing schedules were set for these regimens based on a literature review and expert CRC oncologist input. Each chemotherapeutic regimen was broken down into its component agents, and regimen costs were calculated by summing the costs of each agent per regimen. Price-per-milligram costs were calculated from Health Care Financing Administration Common Procedural Coding System codes for specific drugs. Patient population, temporal, and regional trends were studied among standard regimens. RESULTS: The most common regimens were 5-fluorouracil-leucovorin calcium (5-FU/LV) (147 patients [34.9%]), fluorouracil-leucovorin-irinotecan hydrochloride (FOLFIRI) (111 patients [26.4%]), and fluorouracil-leucovorin-oxaliplatin (103 patients [24.5%]). The remaining 60 patients (14.3%) received irinotecan, capecitabine, and oxaliplatin; oxaliplatin; irinotecan in combination with oxaliplatin; or a miscellaneous regimen. The largest cost differential for 6 cycles of planned treatment was $35,971 between FOLFIRI ($36,999) and 5-FU/LV ($1028). On a per-week basis, treatment costs may differ by more than 91 times. Patient utilization of growth factors, ancillary medications, and monoclonal antibodies added significant costs. CONCLUSIONS: The costs of CRC regimens varied considerably. Trends in treatment regimens have changed notably over time, with newer agents and supportive drugs adding substantially to treatment costs.

The costs of drugs used to treat myelodysplastic syndromes following National Comprehensive Cancer Network Guidelines.

Guidelines for management of patients with myelodysplastic syndromes (MDS) have been generated by the National Comprehensive Cancer Network (NCCN) Myelodysplastic Syndromes Panel. Because MDS is a heterogeneous spectrum of disorders, these patients have been categorized into prognostic subgroups, predominantly using the International Prognostic Scoring System (IPSS). Several drugs have been used to treat these patients, and their selection and sequential recommended use by the panel depend on disease characteristics and responses to treatment. Recombinant erythropoietin alfa and darbepoetin alfa have been the mainstay of therapy for treating anemia associated with MDS. The FDA has recently approved several other drugs for treating MDS, including azacytidine and decitabine for all stages of disease, lenalidomide for low-risk anemic patients with del(5q) chromosomal abnormality, and deferasirox for treating iron overload. For iron chelation, deferoxamine is also used occasionally. Treatment with immunosuppressive therapy (antithymocyte globulin and cyclosporin) has been therapeutically beneficial for a subset of younger patients with MDS. Because the financial cost of these therapies are substantial and have received only limited attention, this article evaluates the costs of specific drugs and their sequential use in the lower-risk IPSS (low and intermediate-1) subgroups based on the NCCN guidelines. Results estimate an average annual cost for potentially anemia-altering drugs of $63,577 per patient, ranging from $26,000 to $95,000, depending on the specific therapies. In patients for whom the therapies fail, annual costs for iron chelation plus red blood cell transfusions are estimated to average $41,412. The economic impact of drug therapy should be weighed against the patient's potential for improvement in clinical outcomes, quality of life, and transfusion requirements.

Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy.

OBJECTIVES: Neutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7-12 days after chemotherapy, and a pegylated form of G-CSF pegfilgrastim, administered once per cycle. METHODS: A cost-utility model based on standard clinical practice of treating FN with immediate hospitalization or with ambulatory treatment, from a societal perspective was developed. Direct medical cost estimates for hospitalization were derived from claims data reported by 115 US academic medical centers. Indirect medical costs, productivity costs, probabilities, and utilities are based on published literature. Results were subjected to sensitivity analyses and 95% confidence intervals are based on a Monte Carlo simulation. RESULTS: Mean estimated costs/day of hospitalization were $1984 (SD $1040, N = 24,687) for surviving patients and $3139 (SD $2014, N = 1437) for dying patients. Under baseline conditions, pegfilgrastim dominated both filgrastim and no G-CSF, with expected costs and effectiveness of $4203 and 12.361 quality adjusted life-days (QALDs) for no G-CSF, $3058 and 12.967 QALDs for pegfilgrastim, and $5264 and 12.698 QALDs for filgrastim. CONCLUSIONS: This cost-utility analysis provides strong evidence that pegfilgrastim is not only cost-effective but also cost-saving in most common clinical and economic settings. There appear to be both clinical and economic benefits from prophylactic administration of pegfilgrastim.

Comparison of beta-lactam and macrolide combination therapy versus fluoroquinolone monotherapy in hospitalized Veterans Affairs patients with community-acquired pneumonia.

Data comparing the treatment outcomes of the two most frequently recommended empirical antibiotic regimens for community-acquired pneumonia (CAP)--combination therapy with an extended-spectrum beta-lactam and a macrolide (BL+M) or fluoroquinolone (F) monotherapy--for patients with severe CAP are sparse. The purpose of this study was to compare empirical BL+M combination therapy with F monotherapy for Veterans Affairs (VA) patients with severe CAP. This retrospective study included patients with CAP who received empirical therapy with BL+M or F between October 1999 and May 2003 in the Upstate New York VA Network. Outcome measures were 14-day mortality, 30-day mortality, and length of hospital stay (LOS). Severe CAP was defined as a class V pneumonia severity index (PSI). During the study period, 261 patients received BL+M and 254 received F. Disease severity was similar for the two treatment groups at admission, and the presence of tachycardia was the only difference noted. For PSI class V patients, there were lower 14-day and 30-day mortality rates with BL+M than with F (14-day rates, 8.2% versus 26.8% [P = 0.02]; 30-day rates, 18.4% versus 36.6% [P = 0.05]). No differences in mortality between treatment groups were noted for the lower PSI classes. The overall median LOS was significantly longer for the BL+M combination group than for the F monotherapy group (6.0 days versus 5.0 days, respectively [P = 0.01]), but no difference in LOS was noted among PSI class V patients. Our study showed that improved outcomes may be realized with BL+M in cases of severe CAP. A randomized clinical study is warranted based on these results.

Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective.

BACKGROUND: The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) reduces the severity and duration of neutropenia and reduces the incidence of febrile neutropenia after cancer chemotherapy. However, the use of G-CSFs, particularly filgrastim, to treat established neutropenia remains controversial. A recent meta-analysis of randomised controlled trials (RCTs) evaluating G-CSF treatment for established febrile neutropenia demonstrated a reduction in prolonged hospitalisations. Because more than one-third of patients in the analysis were hospitalised for at least 10 days, this finding has broad pharmacoeconomic and clinical significance. This analysis presents the potential cost implications of G-CSF treatment for established neutropenia among hospitalised patients. METHODS: Direct medical costs ($US, year 2003 values) related to hospitalisation for established neutropenia were modelled using a hospital perspective and according to two treatment options: (i) no use of G-CSF during the neutropenic episode (control); and (ii) addition of daily G-CSF until neutrophil recovery. Within each option, we modelled the probability of a long stay (>or=10 days) and patient survival. The model used three data sets: discharge data from a consortium of academic medical institutions, drug cost data (filgrastim) from Federal payers, and estimates of G-CSF efficacy derived from a meta-analysis of RCTs of treatment in patients with established febrile neutropenia. The lowest expected total cost was predicted for both treatment options; sensitivity analyses and Monte Carlo simulations were used to evaluate the robustness of the model. RESULTS: The G-CSF arm produced the lowest expected cost, and predicted net estimated savings of $US1046 per neutropenic episode compared with the control strategy. G-CSF was less expensive than the control for most reasonable estimates of cost per day and all lengths of stay (LOS) >or=10 days. G-CSF was the least costly strategy for 73.5% of 10,000 Monte Carlo iterations, while the no-G-CSF control strategy predicted savings in 26.5% of iterations. CONCLUSIONS: This pharmacoeconomic model suggests that therapeutic use of G-CSF should be considered for patients with established neutropenia in order to reduce overall hospital cost. G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions. Therapeutic G-CSF use among patients hospitalised for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes.

Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies.

BACKGROUND: The prognostic accuracy for distant recurrence-free survival using a 21-gene reverse-transcriptase polymerase chain reaction (RT-PCR) assay underwent validation in 668 lymph node-negative, estrogen receptor-positive women with early-stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program (NSABP) B-14. The predictive accuracy for treatment efficacy also underwent validation in 651 patients randomized on NSABP B-20 and 645 patients on NSABP B-14. METHODS: Patients were classified as high (recurrence score [RS] >or= 31), intermediate (RS 18-30), or low (RS < 18) risk for distant recurrence at 10 years. Cost-effectiveness ratios were estimated for RS-guided treatment compared with either tamoxifen alone or the combined chemotherapy and tamoxifen. RESULTS: Distant recurrence was reported in RS low-risk, intermediate-risk, and high-risk patients at 10 years in 3.7%, 17.8%, and 38.3% receiving tamoxifen alone and 5.0%, 10.1%, and 11.1% receiving the chemotherapy and tamoxifen. RS-guided therapy is associated with a gain in individual life expectancy of 2.2 years compared with tamoxifen alone, whereas it is associated with similar life expectancy to that seen with the chemotherapy and tamoxifen strategy. RS-guided therapy is estimated to provide a net cost savings of $2256 compared with chemotherapy and tamoxifen with an incremental cost-effectiveness ratio of $1944 per life year saved compared with tamoxifen alone. CONCLUSIONS: Treatment decisions based on RS-guided therapy compared with tamoxifen alone are associated with greater efficacy with acceptable cost-effectiveness ratios, and associated with similar efficacy and lower cost compared with chemotherapy and tamoxifen for patients with lymph node-negative, estrogen receptor-positive early-stage breast cancer.